E3 ligase TRIM72 negatively regulates myogenesis by IRS-1 ubiquitination
|
|
|
- Magdalene Casey
- 6 years ago
- Views:
Transcription
1 E3 ligase negatively regulates myogenesis by IRS-1 ubiquitination Young-Gyu Ko College of Life Science and Biotechnology Korea University MyHC immunofluorescence
2 Lipid rafts are plasma membrane compartments composed of cholesterol and glycosphingolipids.
3 Insulin action through lipid rafts Signaling molecules found in lipid rafts; IR, IRS, Grb2, Sos, Ras, PI-3-K, TC10, Cbl, CAP, and GLUT4
4 Identification of novel signaling molecules by lipid raft proteome 지질래프트는신호전달물질을농축하고있어서새로운신호전달물질의동정에매우유리
5 Functional proteomics of lipid rafts
6 Functional proteomics of lipid rafts The function of Cell Death Differ, 2010 Lipid raft proteome papers in our lab, gc1qr, surface OXPHOS JBC, 2011; a paper of the week Expert Rev. Proteomics, 2010 CDD, 2010 BBRC, 2010 Proteomics, 2010; cover paper Proteomics, 2009; issue paper Proteomics, 2006; cover paper, 51 citations Diabetologia, 2006; 82 citations EMM, 2004; 66 citations Proteomics, 2004; 30 citations Proteomics, 2004; 108 citations
7 C2C12 Myogenesis Myoblasts Myotubes Myosin Heavy Chain
8 is found in the lipid rafts of C2C12 myotubes. Lee et al., CDD, 2010
9 gene analysis Myoblasts Myotubes Tripartite Motif (TRIM) E3 ligase activity SPla and RYanodine receptor domain Lee et al., CDD, 2010
10 is specifically expressed in skeletal and cardiac muscle 4.4 Kb 2.4 Kb Cav-3 Lee et al., CDD, 2010
11 is highly expressed during C2C12 myogenesis days after differentiation Cav-3 Cav-3 Myogenin Myogenin MyoD MHC MHC Actin Myostatin MyoD Myf5 IRS-1 Coomasie Staining Lee et al., CDD, 2010
12 is a myogenesis inhibitor Lee et al., CDD, 2010
13 What is a molecular target of in IGF signaling?
14 blocks Akt activation in IGF signaling. Ad-EV Ad Si-Con Si mins after IGF activation p-akt IGF Akt IGFR p-mapk IRS-1 MAPK PI-3-K Myoblast Myotube Actin p-akt mtor Hypertrophy Lee et al., CDD, 2010
15 supresses IRS-1 phosphorylation by IGF mins after IGF activation Ad-EV Ad-TRIM Ad-EV Ad-TRIM Ad-EV Ad-TRIM Si-Con Si-TRIM Si-Con Si-TRIM Si-Con Si-TRIM c pakt Akt IP, IGFR; IB, ptyr IP: IRS-1; IB, ptyr IGF IGFR IRS-1 IP: IRS-1; IB, IGFR PI-3-K IP: IRS-1; IB, PI-3K p-akt Myotube Myoblast IP: IGFR; IB, IGFR IP: IRS-1; IB, IRS-1 mtor Hypertrophy Lee et al., CDD, 2010
16 Molecular association of with IRS-1 WCL Mock Ab mins after IGF activation IP: anti-irs1 IRS-1 IGF IGFR IP: anti-cemi IRS-1 IRS-1 PI-3-K p-akt mtor Hypertrophy Lee et al., CDD, 2010
17 negatively regulates myogenesis via targeting IRS-1. Lee et al., CDD, 2010
18 E3 ligase activity??? Protein Ubiquitination
19 Ring Finger domain of Consensus Sequence of Ring Finger Domain, Zn 2+ binding site CX 2 CX (9-39) CX (1-3) HX (2-3) C/HX 2 CX (4-48) CX 2 C sequence MSAAPGLLHQELSCPLCLQLFDAPVTAECGHSFCRACLGRVAGEPAADGTVLC PCCQAPTRPQALSTNLQLARLVEGLAQVPQGHCEEHLDPLSIYCEQDRALVCGV CASLGSHRGHRLLPAAEAHARLKTQLPQQKLQLQEACMRKEKSVAVLEHQLVV EETVRQFRGAVGEQLGKMRVFLAALEGSLDCEAERVRGEAGVALRRELGSLNS YLEQLRQMEKVLEEVADKPQTEFLMKYCLVTSRLQKILAESPPPARLDIQLPIISD DFKFQVWRKMFRALMPALEELTFDPSSAHPSLVVSSSGRRVECSEQKAPPAGED PRQFDKAVAVVAHQQLSEGEHYWEVDVGDKPRWALGVIAAEAPRRGRLHAVPS QGLWLLGLREGKILEAHVEAKEPRALRSPERRPTRIGLYLSFGDGVLSFYDASD ADALVPLFAFHERLPRPVYPFFDVCWHDKGKNAQPLLLVGPEGAEA C 14 C 17 C 29 H 31 C 34 C 37 C 53 C 56 Zn 2+ Zn 2+ C14A mutant? RING mutant?
20 RING domain of is essential for the negative regulation of myogenesis. AD-LacZ AD-TRIM AD-C14A AD- R 20 µm Myogenic index (%) ** * : < 0.01 ** : < 0.05 * ** MyHC Caveolin-3 Myogenin IRS-1 Actin C2C12 myotubes
21 RING domain of is required for the negative regulation of IGF signaling IGF-1 (min) pakt Akt perk1/2 WCL Erk1/2 IRS-1 Actin IP:IRS-1, IB:pY IGF IGFR IRS-1 PI-3-K IP:IRS-1, IB:IRS-1 IP:IRS-1, IB:PI3K IP:IGFR, IB:IRS-1 IP:IGFR, IB:pY IB:IGFR, IB:IGFR p-akt mtor Hypertrophy C2C12 myoblasts
22 RING domain-lacking mutants work as dominant negative forms of endogenous Myc-TRIM Flag-TRIM Flag-C14A Myc-TRIM Flag- R IP: Myc, IB: Myc IP: Myc, IB: Myc IP: Myc, IB: Flag IP: Myc, IB: Flag IP: Flag, IB: Flag IP: Flag, IB: Flag IP: Flag, IB: Myc IP: Flag, IB: Myc IB: Myc (WCL) IB: Myc (WCL) IB: Flag (WCL) IB: Flag (WCL) oligomerization HEK 293 cells
23 RING domain does not prevent binding of to IRS-1 Differentiation days A IRS-1 mrna Actin mrna Flag-IRS-1 Myogenin MyHC Cav-3 IP:Flag, IB:Flag IP:Flag, IB:HA IP:HA, IB:Flag IP:HA, IB:HA IRS-1 IB:Flag (WCL) Actin IB:HA (WCL) C2C12 cells HEK 293 cells
24 RING domain of is required for IRS-1 degradation MG132 Flag-hIRS-1 HA-h IB : Flag IB : HA MG MG Flag-hIRS-1 HA-h IB: Flag IB: HA IRS-1 Expression Level (%) Flag-hIRS-1 HA-h MG132 HEK 293 cells
25 RING domain of is required for IRS-1 ubiquitination HA-TRIM HA-C14A HA- R Flag-IRS-1 His-Ub IP, α-flag; IB, α-his IP, α-flag; IB, α-flag IB: α-ha (WCL) IB: α-flag (WCL) In the presence of MG132 HEK 293 cells
26 RING domain of is required for IRS-1 ubiquitination. -MG132 +MG si-control si- IRS-1 IRS-1 IP: α-irs-1 IB: α-ub IP: α-irs-1 IB: α-ub C2C12 Myoblasts IP: α-irs-1 IB: α-irs-1 IP: α-irs-1 IB: α-irs-1 C2C12 Myotubes
27 disruption enhances MyoD-driven myogenesis in MEFs. WT KO Differentiation days MyoD Myogenin Caveolin-3 MyHC IRS-1 Actin Nuclei No WT KO MyoD Caveolin-3 Myogenin MyHC 0 WT KO IRS-1 Actin MyoD-driven myotubes from +/+ and -/- MEFs
28 disruption abolishes IRS-1 ubiquitination in MyoD-driven myotubes of MEFs MG132 WT KO WT KO IRS-1 IP: α-irs-1 IB: α-ub IP: α-irs-1 IB: α-irs-1 MyoD-driven myotubes from +/+ and -/- MEFs
29 E3 ligase activity??? Protein Ubiquitination
30 UbcH2 mrna and protein are increased during C2C12 myogenesis Differentiation days UbcH2 UbcH3 UbcH5b UbcH6 UbcH2/GAPDH ** * Real-time PCR UbcH7 UbcH8 UbcH10 Ubc Differentiation days Differentiation days UBCH2 Ubc13 Cav-3 Mgn MyHC IRS1 MyoD Cav-3 GAPDH Actin
31 Molecular association of with UbcH2 IP:MBP IB:His IB:MBP IB:His Purified and E2 enzymes In vitro binding assay
32 Molecular association of with UbcH Flag-UbcH Myc-WT Flag Myc Myc Flag Flag Myc WCL IP:IMyc IP:IFlag UbcH2 UbcH2 IP: IP: UbcH2 Exogenous IP in 293 cells Endogenous IP in C2C12 myotubes
33 UbcH2 knockdown enhances myogenesis by inhibiting IRS-1 ubiquitination. Si-control Si-UbcH Si-control Si-UbcH2 Myogenic index (%) * UbcH2 MyHC Cav-3 Mgn IRS-1 UbcH2 IRS-1 WCL Ubiquitin IRS-1 IP:IRS-1 Actin C2C12 myotubes
34 inhibition of myogenesis is released by UbcH2 knockdown Si-control HA- Si-UbcH2 HA si-control HA- si-ubch2 HA- The number of nucleus In HA-positive cells MyHC HA DAPI C2C12 myotubes
35 is highly expressed in soleus muscle. soleus gastrocnemius Color Red muscle White muscle Size Smaller Larger Fatigue Resistant High Sensitive Low Jung and Ko, BBRC, 2010
36 Skeletal muscle size is increased in -disrupted mice * <0.05 Weight (mg) WT WT KO KO Percentage (%) WT KO 2.0 Cross Sectioned Area (mm 2 ) Mouse soleus muscle
37 IRS-1 expression level is elevated in TRIM-disrupted skeletal muscle WT - + KO - + Insulin Insulin (min) pakt Akt perk Erk Actin IRS-1 pakt Akt perk ERK Actin C2C12 Myoblasts py IRS-1 IP:IRS-1 Mouse soleus muscle
38 is a therapeutic target for type 2 diabetes Plasma glucose (mg/dl) Glucose tolerance test WT KO *p<0.05 * * Time (min) Plasma glucose (% reduction) 120 * Insulin tolerance test *p<0.05 * * WT KO Time (min) High fat diet-fed mice
39 E3 ligase negatively regulates myogenesis by IRS-1 ubiquitination. by Ub
40 Suggestion; is a negative muscle size regulator.
41 Korea University Lab of Cell Signal Transduction Dr. Jae-Sung Yi Dr. Chang-Seok Lee Dr. Young-Mi Ham Miss Na-Rae Lee Ms. Nga Nguyen Mr. Jing Hong Mr. June-Seop Lee Mr. Jeong-Woo Lee Mr. Dong-Min Yoo
A Central Role of MG53 in Metabolic Syndrome. and Type-2 Diabetes
A Central Role of MG53 in Metabolic Syndrome and Type-2 Diabetes Yan Zhang, Chunmei Cao, Rui-Ping Xiao Institute of Molecular Medicine (IMM) Peking University, Beijing, China Accelerated Aging in China
SUPPLEMENTARY INFORMATION
doi:10.1038/nature12652 Supplementary Figure 1. PRDM16 interacts with endogenous EHMT1 in brown adipocytes. Immunoprecipitation of PRDM16 complex by flag antibody (M2) followed by Western blot analysis
Supplementary Figure 1.TRIM33 binds β-catenin in the nucleus. a & b, Co-IP of endogenous TRIM33 with β-catenin in HT-29 cells (a) and HEK 293T cells
Supplementary Figure 1.TRIM33 binds β-catenin in the nucleus. a & b, Co-IP of endogenous TRIM33 with β-catenin in HT-29 cells (a) and HEK 293T cells (b). TRIM33 was immunoprecipitated, and the amount of
RAW264.7 cells stably expressing control shrna (Con) or GSK3b-specific shrna (sh-
1 a b Supplementary Figure 1. Effects of GSK3b knockdown on poly I:C-induced cytokine production. RAW264.7 cells stably expressing control shrna (Con) or GSK3b-specific shrna (sh- GSK3b) were stimulated
Enhancement of C2C12 myoblast proliferation and differentiation by diarylheptanoid form Curcuma comosa Roxb.
Enhancement of C2C12 myoblast proliferation and differentiation by diarylheptanoid form Curcuma comosa Roxb. Curcuma comosa Roxb. Mr. Chittipong Tipbunjong Mahidol University Bangkok, Thailand Muscle regeneration
Supplementary Figure 1. DJ-1 modulates ROS concentration in mouse skeletal muscle.
Supplementary Figure 1. DJ-1 modulates ROS concentration in mouse skeletal muscle. (a) mrna levels of Dj1 measured by quantitative RT-PCR in soleus, gastrocnemius (Gastroc.) and extensor digitorum longus
Supplementary Fig. 1. GPRC5A post-transcriptionally down-regulates EGFR expression. (a) Plot of the changes in steady state mrna levels versus
Supplementary Fig. 1. GPRC5A post-transcriptionally down-regulates EGFR expression. (a) Plot of the changes in steady state mrna levels versus changes in corresponding proteins between wild type and Gprc5a-/-
SUPPLEMENTARY INFORMATION
SUPPLEMENTARY INFORMATION doi:1.138/nature9814 a A SHARPIN FL B SHARPIN ΔNZF C SHARPIN T38L, F39V b His-SHARPIN FL -1xUb -2xUb -4xUb α-his c Linear 4xUb -SHARPIN FL -SHARPIN TF_LV -SHARPINΔNZF -SHARPIN
CYLD Negatively Regulates Transforming Growth Factor-β Signaling via Deubiquitinating Akt
Supplementary Information CYLD Negatively Regulates Transforming Growth Factor-β Signaling via Deubiquitinating Akt Jae Hyang Lim, Hirofumi Jono, Kensei Komatsu, Chang-Hoon Woo, Jiyun Lee, Masanori Miyata,
Supplementary Information
Supplementary Information mediates STAT3 activation at retromer-positive structures to promote colitis and colitis-associated carcinogenesis Zhang et al. a b d e g h Rel. Luc. Act. Rel. mrna Rel. mrna
Supplementary Figure 1: si-craf but not si-braf sensitizes tumor cells to radiation.
Supplementary Figure 1: si-craf but not si-braf sensitizes tumor cells to radiation. (a) Embryonic fibroblasts isolated from wildtype (WT), BRAF -/-, or CRAF -/- mice were irradiated (6 Gy) and DNA damage
Peli1 negatively regulates T-cell activation and prevents autoimmunity
Peli1 negatively regulates T-cell activation and prevents autoimmunity Mikyoung Chang 1,*, Wei Jin 1,5,*, Jae-Hoon Chang 1, Yi-chuan Xiao 1, George Brittain 1, Jiayi Yu 1, Xiaofei Zhou 1, Yi-Hong Wang
Novel Physiological Role of Caveolin-1 in Aging and Aging-related Diseases. Sang Chul Park Gachon University Lee Gil Ya Cancer and Diabetes Institute
Novel Physiological Role of Caveolin-1 in Aging and Aging-related Diseases Sang Chul Park Gachon University Lee Gil Ya Cancer and Diabetes Institute Primarily I asked questions on biological issues on
IL-6 - a hypertrophic factor
IL-6 - a hypertrophic factor 3 rd CIM PhD Course Copenhagen, April 30 th, 2009 Pompeu Fabra University Department of Experimental and Health Sciences Barcelona, Spain Myogenesis MRF: muscle regulatory
9/16/2009. Fast and slow twitch fibres. Properties of Muscle Fiber Types Fast fibers Slow fibers
Muscles, muscle fibres and myofibrils Fast and slow twitch fibres Rat hindlimb muscle ATPase staining at different ph and NADH Muscle fibre shortening velocity lengths/second Properties of Muscle Fiber
Reviewers' comments: Reviewer #1 (Remarks to the Author):
Reviewers' comments: Reviewer #1 (Remarks to the Author): In this manuscript, Song et al. identified FBXW7 as a new positive regulator for RIG-Itriggered type I IFN signaling pathway. The authors observed
Supplementary Figure 1 Chemokine and chemokine receptor expression during muscle regeneration (a) Analysis of CR3CR1 mrna expression by real time-pcr
Supplementary Figure 1 Chemokine and chemokine receptor expression during muscle regeneration (a) Analysis of CR3CR1 mrna expression by real time-pcr at day 0, 1, 4, 10 and 21 post- muscle injury. (b)
Supplemental Information. Metabolic Maturation during Muscle Stem Cell. Differentiation Is Achieved by mir-1/133a-mediated
Cell Metabolism, Volume 27 Supplemental Information Metabolic Maturation during Muscle Stem Cell Differentiation Is Achieved by mir-1/133a-mediated Inhibition of the Dlk1-Dio3 Mega Gene Cluster Stas Wüst,
SUPPLEMENTAL FIGURE LEGENDS
SUPPLEMENTAL FIGURE LEGENDS Supplemental Figure S1: Endogenous interaction between RNF2 and H2AX: Whole cell extracts from 293T were subjected to immunoprecipitation with anti-rnf2 or anti-γ-h2ax antibodies
Regulation of Lipid Homeostasis: Lipid Droplets
Regulation of Lipid Homeostasis: Lipid Droplets Bernd Helms Article Brand Recter Hendrik Mertens 1 The Basics I: FAs The Basics II: FA Activation 2 Basics III: TG-FA Interplay. Why? Adipocytes 3 Foam cells
supplementary information
DOI: 10.1038/ncb1875 Figure S1 (a) The 79 surgical specimens from NSCLC patients were analysed by immunohistochemistry with an anti-p53 antibody and control serum (data not shown). The normal bronchi served
SUPPLEMENTARY INFORMATION
doi: 10.1038/nature05732 SUPPLEMENTARY INFORMATION Supplemental Data Supplement Figure Legends Figure S1. RIG-I 2CARD undergo robust ubiquitination a, (top) At 48 h posttransfection with a GST, GST-RIG-I-2CARD
ACC ELOVL MCAD. CPT1α 1.5 *** 0.5. Reverbα *** *** 0.5. Fasted. Refed
Supplementary Figure A 8 SREBPc 6 5 FASN ELOVL6.5.5.5 ACC.5.5 CLOCK.5.5 CRY.5.5 PPARα.5.5 ACSL CPTα.5.5.5.5 MCAD.5.5 PEPCK.5.5 G6Pase 5.5.5.5 BMAL.5.5 Reverbα.5.5 Reverbβ.5.5 PER.5.5 PER B Fasted Refed
Master class Biomolecular Sciences Molecular Cell Biology.
Master class Biomolecular Sciences Molecular Cell Biology. 04-09-08: Paul van Bergen en Henegouwen. Clathrin-indep Endocytosis 11-09-08: Willem Stoorvogel. Endocytosis and MHC classii 18-09-08: X-track
TRAF6 regulates satellite stem cell self-renewal and function during regenerative myogenesis
The Journal of Clinical Investigation TRAF6 regulates satellite stem cell self-renewal and function during regenerative myogenesis Sajedah M. Hindi and Ashok Kumar Department of Anatomical Sciences and
Supplementary Materials for
www.sciencesignaling.org/cgi/content/full/9/439/ra78/dc1 Supplementary Materials for Small heterodimer partner mediates liver X receptor (LXR) dependent suppression of inflammatory signaling by promoting
Insulin and IGF-1 receptors regulate FoxOmediated signaling in muscle proteostasis
Insulin and IGF-1 receptors regulate FoxOmediated signaling in muscle proteostasis Brian T. O Neill,, K. Sreekumaran Nair, C. Ronald Kahn J Clin Invest. 2016;126(9):3433-3446. https://doi.org/10.1172/jci86522.
Supplementary Figure S1 Supplementary Figure S2
Supplementary Figure S A) The blots shown in Figure B were qualified by using Gel-Pro analyzer software (Rockville, MD, USA). The ratio of LC3II/LC3I to actin was then calculated. The data are represented
Supplementary Figure 1. Spatial distribution of LRP5 and β-catenin in intact cardiomyocytes. (a) and (b) Immunofluorescence staining of endogenous
Supplementary Figure 1. Spatial distribution of LRP5 and β-catenin in intact cardiomyocytes. (a) and (b) Immunofluorescence staining of endogenous LRP5 in intact adult mouse ventricular myocytes (AMVMs)
STARS. Mini-Symposium. Skeletal Muscle: Development, Adaptation & Disease. Gain Without Pain
STARS Mini-Symposium Skeletal Muscle: Development, Adaptation & Disease Gain Without Pain Rhonda Bassel-Duby, Ph.D. Associate Professor of Molecular Biology Diagram of Skeletal Muscle Myoglobin Immunohistochemistry
Syntaxin 4 regulates the surface localization of a promyogenic receptor Cdo thereby promoting myogenic differentiation
Yoo et al. Skeletal Muscle (2015) 5:28 DOI 10.1186/s13395-015-0052-8 RESEARCH Open Access Syntaxin 4 regulates the surface localization of a promyogenic receptor Cdo thereby promoting myogenic differentiation
Muscles, muscle fibres and myofibrils
Muscles, muscle fibres and myofibrils Properties of Muscle Fiber Types Fast fibers Slow fibers Characteristic IIb IIx IIa Type I V max (speed of shortening) Highest Intermediate Low Resistance to fatigue
Supplementary Figure 1 CD4 + T cells from PKC-θ null mice are defective in NF-κB activation during T cell receptor signaling. CD4 + T cells were
Supplementary Figure 1 CD4 + T cells from PKC-θ null mice are defective in NF-κB activation during T cell receptor signaling. CD4 + T cells were isolated from wild type (PKC-θ- WT) or PKC-θ null (PKC-θ-KO)
Complexity DNA. Genome RNA. Transcriptome. Protein. Proteome. Metabolites. Metabolome
DNA Genome Complexity RNA Transcriptome Systems Biology Linking all the components of a cell in a quantitative and temporal manner Protein Proteome Metabolites Metabolome Where are the functional elements?
Molecular Medicine. Angiotensin II Induces Skeletal Muscle Atrophy by Activating TFEB-Mediated MuRF1 Expression
Molecular Medicine Angiotensin II Induces Skeletal Muscle Atrophy by Activating TFEB-Mediated MuRF1 Expression Philipp Du Bois, Cristina Pablo Tortola, Doerte Lodka, Melanie Kny, Franziska Schmidt, Kunhua
TRAF6 ubiquitinates TGFβ type I receptor to promote its cleavage and nuclear translocation in cancer
Supplementary Information TRAF6 ubiquitinates TGFβ type I receptor to promote its cleavage and nuclear translocation in cancer Yabing Mu, Reshma Sundar, Noopur Thakur, Maria Ekman, Shyam Kumar Gudey, Mariya
Supplementary Figure 1
VO (ml kg - min - ) VCO (ml kg - min - ) Respiratory exchange ratio Energy expenditure (cal kg - min - ) Locomotor activity (x count) Body temperature ( C) Relative mrna expression TA Sol EDL PT Heart
Gallic acid prevents isoproterenol-induced cardiac hypertrophy and fibrosis through regulation of JNK2 signaling and Smad3 binding activity
Gallic acid prevents isoproterenol-induced cardiac hypertrophy and fibrosis through regulation of JNK2 signaling and Smad3 binding activity Yuhee Ryu 1,+, Li Jin 1,2+, Hae Jin Kee 1,, Zhe Hao Piao 3, Jae
(A) SW480, DLD1, RKO and HCT116 cells were treated with DMSO or XAV939 (5 µm)
Supplementary Figure Legends Figure S1. Tankyrase inhibition suppresses cell proliferation in an axin/β-catenin independent manner. (A) SW480, DLD1, RKO and HCT116 cells were treated with DMSO or XAV939
An HMGA2-IGF2BP2 Axis Regulates Myoblast Proliferation and Myogenesis
Please cite this article in press as: Li et al., An HMGA2-IGF2BP2 Axis Regulates Myoblast Proliferation and Myogenesis, Developmental Cell (2012), http://dx.doi.org/10.1016/j.devcel.2012.10.019 Developmental
GW(g)/BW(g) GW(g)/BW(g) Con Dex Con Dex. GW(g)/BW(g) Relative mrna levels. Atrogin-1 Murf-1. Atrogin-1 Murf-1. Soleus
a b c GW(g) GW(g) GW(g) 0.20 0.15 0.10 0.05 0.00 0.20 0.15 0.10 0.05 Den * ** GW(g)/BW(g) Den Dex Dex GW(g)/BW(g) d 0.00 Fasting GW(g) e 0.15 Cancer Cachexia f GW(g) 0.10 0.05 0.00 Young ** Old g GW(g)/BW(g)
Supplemental Figure 1. (A) The localization of Cre DNA recombinase in the testis of Cyp19a1-Cre mice was detected by immunohistchemical analyses
Supplemental Figure 1. (A) The localization of Cre DNA recombinase in the testis of Cyp19a1-Cre mice was detected by immunohistchemical analyses using an anti-cre antibody; testes at 1 week (left panel),
SUPPLEMENTARY INFORMATION
DOI:.38/ncb2822 a MTC02 FAO cells EEA1 b +/+ MEFs /DAPI -/- MEFs /DAPI -/- MEFs //DAPI c HEK 293 cells WCE N M C P AKT TBC1D7 Lamin A/C EEA1 VDAC d HeLa cells WCE N M C P AKT Lamin A/C EEA1 VDAC Figure
HSP72 HSP90. Quadriceps Muscle. MEF2c MyoD1 MyoG Myf5 Hsf1 Hsp GLUT4/GAPDH (AU)
Supplementary Figure 1. Impaired insulin action in HSP72 deficient muscle and myotubes in culture cannot be explained by altered myogenesis or reduced total GLUT4 expression. Genes associated with myogenesis
Supplementary Table 1.
Supplementary Table 1. Expression of genes involved in brown fat differentiation in WAT of db/db mice treated with HDAC inhibitors. Data are expressed as fold change (FC) versus control. symbol FC SAHA
Supplementary Figure 1. PAQR3 knockdown inhibits SREBP-2 processing in CHO-7 cells CHO-7 cells were transfected with control sirna or a sirna
Supplementary Figure 1. PAQR3 knockdown inhibits SREBP-2 processing in CHO-7 cells CHO-7 cells were transfected with control sirna or a sirna targeted for hamster PAQR3. At 24 h after the transfection,
TRPM8 in the negative regulation of TNFα expression during cold stress
in the negative regulation of TNFα expression during cold stress Xin-Pei Wang 1, Xuan Yu 1, Xiao-Jin Yan 1, Fan Lei 2, Yu-Shuang Chai 1, Jing-Fei Jiang 1, Zhi- Yi Yuan 1, Dong-Ming Xing 1, Li-Jun Du 1*
FH- FH+ DM. 52 Volunteers. Oral & IV Glucose Tolerance Test Hyperinsulinemic Euglycemic Clamp in Non-DM Subjects ACADSB MYSM1. Mouse Skeletal Muscle
A 52 Volunteers B 6 5 4 3 2 FH- FH+ DM 1 Oral & IV Glucose Tolerance Test Hyperinsulinemic Euglycemic Clamp in Non-DM Subjects ZYX EGR2 NR4A1 SRF target TPM1 ACADSB MYSM1 Non SRF target FH- FH+ DM2 C SRF
Supplemental Information. Increased 4E-BP1 Expression Protects. against Diet-Induced Obesity and Insulin. Resistance in Male Mice
Cell Reports, Volume 16 Supplemental Information Increased 4E-BP1 Expression Protects against Diet-Induced Obesity and Insulin Resistance in Male Mice Shih-Yin Tsai, Ariana A. Rodriguez, Somasish G. Dastidar,
Supplemental Information
Supplemental Information Tobacco-specific Carcinogen Induces DNA Methyltransferases 1 Accumulation through AKT/GSK3β/βTrCP/hnRNP-U in Mice and Lung Cancer patients Ruo-Kai Lin, 1 Yi-Shuan Hsieh, 2 Pinpin
T H E J O U R N A L O F C E L L B I O L O G Y
Supplemental material Jewell et al., http://www.jcb.org/cgi/content/full/jcb.201007176/dc1 T H E J O U R N A L O F C E L L B I O L O G Y Figure S1. IR Munc18c association is independent of IRS-1. (A and
condition. Left panel, the HCT-116 cells were lysed with RIPA buffer containing 0.1%
FIGURE LEGENDS Supplementary Fig 1 (A) sumoylation pattern detected under denaturing condition. Left panel, the HCT-116 cells were lysed with RIPA buffer containing 0.1% SDS in the presence and absence
GPR120 *** * * Liver BAT iwat ewat mwat Ileum Colon. UCP1 mrna ***
a GPR120 GPR120 mrna/ppia mrna Arbitrary Units 150 100 50 Liver BAT iwat ewat mwat Ileum Colon b UCP1 mrna Fold induction 20 15 10 5 - camp camp SB202190 - - - H89 - - - - - GW7647 Supplementary Figure
SUPPLEMENTARY INFORMATION
-. -. SUPPLEMENTARY INFORMATION DOI: 1.1/ncb86 a WAT-1 WAT- BAT-1 BAT- sk-muscle-1 sk-muscle- mir-133b mir-133a mir-6 mir-378 mir-1 mir-85 mir-378 mir-6a mir-18 mir-133a mir- mir- mir-341 mir-196a mir-17
Supplementary Figures
Supplementary Figures mir-150 regulates obesityassociated insulin resistance by controlling B cell functions Wei Ying, Alexander Tseng, Richard Cheng-An Chang, Haiqing Wang, Yu-lieh Lin, Srikanth Kanameni,
Title: Cytosolic DNA-mediated, STING-dependent pro-inflammatory gene. Fig. S1. STING ligands-mediated signaling response in MEFs. (A) Primary MEFs (1
1 Supporting Information 2 3 4 Title: Cytosolic DNA-mediated, STING-dependent pro-inflammatory gene induction necessitates canonical NF-κB activation through TBK1 5 6 Authors: Abe et al. 7 8 9 Supporting
Supplementary Figure 1. Confocal immunofluorescence showing mitochondrial translocation of Drp1. Cardiomyocytes treated with H 2 O 2 were prestained
Supplementary Figure 1. Confocal immunofluorescence showing mitochondrial translocation of Drp1. Cardiomyocytes treated with H 2 O 2 were prestained with MitoTracker (red), then were immunostained with
A microrna-34a/fgf21 Regulatory Axis and Browning of White Fat
A microrna-34a/fgf21 Regulatory Axis and Browning of White Fat Jongsook Kim Kemper, Ph.D Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, USA 213 International
Supplementary Information File
Supplementary Information File Supplementary Table 1. List of synthesized sirna sequences for target genes sirna Species Sequence Ctrl sirna mouse sense 5 -UUCUCCGAACGUGUCACGUTT-3 Antisense 5 -ACGUGACACGUUCGGAGAATT-3
Supplemental Table 1: Demographics and characteristics of study participants. Male, n (%) 3 (20%) 6 (50%) Age, years [mean ± SD] 33.3 ± ± 9.
![Supplemental Table 1: Demographics and characteristics of study participants. Male, n (%) 3 (20%) 6 (50%) Age, years [mean ± SD] 33.3 ± ± 9.](/thumbs/90/103696086.jpg "Supplemental Table 1: Demographics and characteristics of study participants. Male, n (%) 3 (20%) 6 (50%) Age, years [mean ± SD] 33.3 ± ± 9.")
SUPPLEMENTAL DATA Supplemental Table 1: Demographics and characteristics of study participants Lean (n=15) Obese (n=12) Male, n (%) 3 (20%) 6 (50%) Age, years [mean ± SD] 33.3 ± 9.5 44.8 ± 9.1 White, n
293T cells were transfected with indicated expression vectors and the whole-cell extracts were subjected
SUPPLEMENTARY INFORMATION Supplementary Figure 1. Formation of a complex between Slo1 and CRL4A CRBN E3 ligase. (a) HEK 293T cells were transfected with indicated expression vectors and the whole-cell
Supporting Information
Supporting Information M1 macrophage-derived nanovesicles potentiate the anticancer efficacy of immune checkpoint inhibitors Yeon Woong Choo, 1, Mikyung Kang, 2, Han Young Kim, 1 Jin Han, 1 Seokyung Kang,
Transcriptional Regulation of Skeletal Muscle Atrophy-Induced Gene Expression by Muscle Ring Finger-1 and Myogenic Regulatory Factors
UNF Digital Commons UNF Theses and Dissertations Student Scholarship 2017 Transcriptional Regulation of Skeletal Muscle Atrophy-Induced Gene Expression by Muscle Ring Finger-1 and Myogenic Regulatory Factors
DISRUPTION OF BRANCHED-CHAIN AMINO ACID CATABOLISM IMPAIRS RAT MYOBLAST SURVIVAL AND DIFFERENTIATION ZAMEER N. DHANANI
DISRUPTION OF BRANCHED-CHAIN AMINO ACID CATABOLISM IMPAIRS RAT MYOBLAST SURVIVAL AND DIFFERENTIATION ZAMEER N. DHANANI A thesis submitted to the Faculty of Graduate Studies in partial fulfillment of the
S1a S1b S1c. S1d. S1f S1g S1h SUPPLEMENTARY FIGURE 1. - si sc Il17rd Il17ra bp. rig/s IL-17RD (ng) -100 IL-17RD
SUPPLEMENTARY FIGURE 1 0 20 50 80 100 IL-17RD (ng) S1a S1b S1c IL-17RD β-actin kda S1d - si sc Il17rd Il17ra rig/s15-574 - 458-361 bp S1f S1g S1h S1i S1j Supplementary Figure 1. Knockdown of IL-17RD enhances
Supplementary Information
Supplementary Information Notch deficiency decreases hepatic lipid accumulation by induction of fatty acid oxidation No-Joon Song,#, Ui Jeong Yun,#, Sunghee Yang, Chunyan Wu, Cho-Rong Seo, A-Ryeong Gwon,,
SUPPLEMENTARY INFORMATION
Supplementary Figures Supplementary Figure S1. Binding of full-length OGT and deletion mutants to PIP strips (Echelon Biosciences). Supplementary Figure S2. Binding of the OGT (919-1036) fragments with
SUPPLEMENTARY LEGENDS...
TABLE OF CONTENTS SUPPLEMENTARY LEGENDS... 2 11 MOVIE S1... 2 FIGURE S1 LEGEND... 3 FIGURE S2 LEGEND... 4 FIGURE S3 LEGEND... 5 FIGURE S4 LEGEND... 6 FIGURE S5 LEGEND... 7 FIGURE S6 LEGEND... 8 FIGURE
ZL ZDF ZDF + E2 *** Visceral (g) ZDF
Body Weight (g) 4 3 2 1 ** * ZL ZDF 6 8 1 12 14 16 Age (weeks) B * Sub-cutaneous (g) 16 12 8 4 ZL ZDF Visceral (g) 25 2 15 1 5 ZL ZDF Total fat pad weight (g) 4 3 2 1 ZDF ZL Supplemental Figure 1: Effect
Professor Christopher Proud
South Australian Health and Medical Research Institute Professor Christopher Proud Cell Signalling & Gene Regulation Professor Christopher G. Proud Nutrition and Metabolism Theme Leader South Australian
Supplementary Figure 1. Blood glucose and insulin levels in mice during 4-day infusion.
Supplementary Figure 1. Blood glucose and insulin levels in mice during 4-day infusion. (A-B) WT and HT mice infused with saline or glucose had overlapping achieved blood glucose and insulin levels, necessitating
Supplementary Materials for
www.sciencesignaling.org/cgi/content/full/6/264/rs4/dc1 Supplementary Materials for A Systems Approach for Decoding Mitochondrial Retrograde Signaling Pathways Sehyun Chae, Byung Yong Ahn, Kyunghee Byun,
A Hepatocyte Growth Factor Receptor (Met) Insulin Receptor hybrid governs hepatic glucose metabolism SUPPLEMENTARY FIGURES, LEGENDS AND METHODS
A Hepatocyte Growth Factor Receptor (Met) Insulin Receptor hybrid governs hepatic glucose metabolism Arlee Fafalios, Jihong Ma, Xinping Tan, John Stoops, Jianhua Luo, Marie C. DeFrances and Reza Zarnegar
The ubiquitin proteasome system in cardiovascular disease Basic mechanisms
ECS Congress 2010 Stockholm, Sweden 28 Aug 2010 01 Sep 2010 The ubiquitin proteasome system in cardiovascular disease Basic mechanisms Saskia Schlossarek Department of Experimental and Clinical Pharmacology
What would you observe if you fused a G1 cell with a S cell? A. Mitotic and pulverized chromosomes. B. Mitotic and compact G1 chromosomes.
What would you observe if you fused a G1 cell with a S cell? A. Mitotic and pulverized chromosomes. B. Mitotic and compact G1 chromosomes. C. Mostly non-compact G1 chromosomes. D. Compact G1 and G2 chromosomes.
SUPPLEMENTARY INFORMATION
a c e doi:10.1038/nature10407 b d f Supplementary Figure 1. SERCA2a complex analysis. (a) Two-dimensional SDS-PAGE gels of SERCA2a complexes. A silver-stained SDSPAGE gel is shown, which reveals a 12 kda
Identification of a role for Janus kinase2 (JAK2) in skeletal muscle mitogenesis, myogenesis, and hypertrophy
Retrospective Theses and Dissertations Iowa State University Capstones, Theses and Dissertations 2005 Identification of a role for Janus kinase2 (JAK2) in skeletal muscle mitogenesis, myogenesis, and hypertrophy
Sphingolipid de novo synthesis: its relevance to metabolic diseases and cell polarity
Sphingolipid de novo synthesis: its relevance to metabolic diseases and cell polarity Xian-Cheng Jiang (shian-chen chiang) SUNY Downstate Medical Center Cell plasma membrane Lipid rafts Sphingolipid =
Effect of BI-1 on insulin resistance through regulation of CYP2E1
Effect of BI-1 on insulin resistance through regulation of CYP2E1 Geum-Hwa Lee 1, Kyoung-Jin Oh 2, 3, Hyung-Ryong Kim 4, Hye-Sook Han 2, Hwa-Young Lee 1, Keun-Gyu Park 5, Ki-Hoan Nam 6, Seung-Hoi Koo 2
Does Pharmacological Exercise Mimetics Exist? Hokkaido University Graduate School of Medicine Shintaro Kinugawa
Does Pharmacological Exercise Mimetics Exist? Hokkaido University Graduate School of Medicine Shintaro Kinugawa Survival rate (%) Peak oxygen uptake and prognosis in patients with heart failure (HF) 1
Supplementary Figure 1
Supplementary Figure 1 Dox Cis Cam Pac 0 15 1 15 1 15 1 15 1 15 µmole/l Ub p53 Cytotoxic anticancer agents increase p53 levels but do not generally promote the accumulation of ubiquitinated. Western blots
c Ischemia (30 min) Reperfusion (8 w) Supplementary Figure bp 300 bp Ischemia (30 min) Reperfusion (4 h) Dox 20 mg/kg i.p.
a Marker Ripk3 +/ 5 bp 3 bp b Ischemia (3 min) Reperfusion (4 h) d 2 mg/kg i.p. 1 w 5 w Sacrifice for IF size A subset for echocardiography and morphological analysis c Ischemia (3 min) Reperfusion (8
GH-Releasing Hormone Promotes Survival and Prevents TNF- -Induced Apoptosis and Atrophy in C2C12 Myotubes
ORIGINAL RESEARCH GH-Releasing Hormone Promotes Survival and Prevents TNF- -Induced Apoptosis and Atrophy in C2C12 Myotubes Davide Gallo,* Iacopo Gesmundo,* Letizia Trovato, Giulia Pera, Eleonora Gargantini,
Nature Immunology: doi: /ni.3866
Nature Immunology: doi:10.1038/ni.3866 Supplementary Figure 1 The effect of TIPE2 on chemotaxis. a, The expression of TIPE2 in dhl-60c, dhl-60t, TIPE2-expressing and 15/16Q-expressing dhl-60t neutrophils
The regulation of 11 β-hydroxysteroid dehydrogenase type 1 by ageing and glucocorticoids in key tissues
The regulation of 11 β-hydroxysteroid dehydrogenase type 1 by ageing and glucocorticoids in key tissues By Dr Mark Sherlock A thesis submitted to the University of Birmingham for the degree of Doctor of
Tumor stage : I II III IV. well differentiated. moderately differentiated. adenocarcinoma. normal colon (adjacent to cancer) Log (T/H) SLAP mrna level
moderately differentiated well differentiated Log (T/H) mrna level a Tumor stage : I II III IV.4.4.8 1.2 1.6 2. 2.4 2.8 3.2 N 1 2 3 4 5 6 7 8 9 1 11 12 13 14 15 16 17 # patient b normal colon (adjacent
Ratchakrit Srikuea 1 and Muthita Hirunsai 2 1
J Appl Physiol 120: 1381 1393, 2016. First published March 31, 2016; doi:10.1152/japplphysiol.01018.2015. Effects of intramuscular administration of 1,25(OH) 2 D 3 during skeletal muscle regeneration on
Intracellular MHC class II molecules promote TLR-triggered innate. immune responses by maintaining Btk activation
Intracellular MHC class II molecules promote TLR-triggered innate immune responses by maintaining Btk activation Xingguang Liu, Zhenzhen Zhan, Dong Li, Li Xu, Feng Ma, Peng Zhang, Hangping Yao and Xuetao
Dynamic Interaction of Stress Granule, DDX3X and IKK-α Mediates Multiple Functions in
Dynamic Interaction of Stress Granule, and Mediates Multiple Functions in Hepatitis C Virus Infection Véronique Pène, Qisheng Li#, Catherine Sodroski, Ching-Sheng Hsu, T. Jake Liang# Liver Diseases Branch,
Supplementary Figure 1. MAT IIα is Acetylated at Lysine 81.
IP: Flag a Mascot PTM Modified Mass Error Position Gene Names Score Score Sequence m/z [ppm] 81 MAT2A;AMS2;MATA2 35.6 137.28 _AAVDYQK(ac)VVR_ 595.83-2.28 b Pre-immu After-immu Flag- WT K81R WT K81R / Flag
Supplementary Table 1. The primers used for quantitative RT-PCR. Gene name Forward (5 > 3 ) Reverse (5 > 3 )
770 771 Supplementary Table 1. The primers used for quantitative RT-PCR. Gene name Forward (5 > 3 ) Reverse (5 > 3 ) Human CXCL1 GCGCCCAAACCGAAGTCATA ATGGGGGATGCAGGATTGAG PF4 CCCCACTGCCCAACTGATAG TTCTTGTACAGCGGGGCTTG
Supplementary Figure 1
Supplementary Figure 1 Supplementary Figure 1. Neither the activation nor suppression of the MAPK pathway affects the ASK1/Vif interaction. (a, b) HEK293 cells were cotransfected with plasmids encoding
Atrogin-1/muscle atrophy F-box inhibits calcineurin-dependent cardiac hypertrophy by participating in an SCF ubiquitin ligase complex
Research article Atrogin-1/muscle atrophy F-box inhibits calcineurin-dependent cardiac hypertrophy by participating in an SCF ubiquitin ligase complex Hui-Hua Li, 1 Vishram Kedar, 1 Chunlian Zhang, 1 Holly
Identified proteins interacting with TMBIM1 by mass spectrometry
Supplementary Information Journal: Nature Medicine Article Title: Corresponding Author: A novel multivesicular body regulator TMBIM1 protects against non-alcoholic fatty liver disease in mice and monkeys
Supplemental Materials. STK16 regulates actin dynamics to control Golgi organization and cell cycle
Supplemental Materials STK16 regulates actin dynamics to control Golgi organization and cell cycle Juanjuan Liu 1,2,3, Xingxing Yang 1,3, Binhua Li 1, Junjun Wang 1,2, Wenchao Wang 1, Jing Liu 1, Qingsong
SUPPLEMENTARY INFORMATION
DOI: 10.1038/ncb3311 A B TSC2 -/- MEFs C Rapa Hours WCL 0 6 12 24 36 pakt.s473 AKT ps6k S6K CM IGF-1 Recipient WCL - + - + - + pigf-1r IGF-1R pakt ps6 AKT D 1 st SILAC 2 nd SILAC E GAPDH FGF21 ALKPGVIQILGVK
hexahistidine tagged GRP78 devoid of the KDEL motif (GRP78-His) on SDS-PAGE. This
SUPPLEMENTAL FIGURE LEGEND Fig. S1. Generation and characterization of. (A) Coomassie staining of soluble hexahistidine tagged GRP78 devoid of the KDEL motif (GRP78-His) on SDS-PAGE. This protein was expressed
GSK3β mediates muscle pathology in myotonic dystrophy
Research article GSK3β mediates muscle pathology in myotonic dystrophy Karlie Jones, 1 Christina Wei, 1 Polina Iakova, 2 Enrico Bugiardini, 3 Christiane Schneider-Gold, 4 Giovanni Meola, 3 James Woodgett,
Supplements. Figure S1. B Phalloidin Alexa488
Supplements A, DMSO, PP2, PP3 Crk-myc Figure S1. (A) Src kinase activity is necessary for recruitment of Crk to Nephrin cytoplasmic domain. Human podocytes expressing /7-NephrinCD () were treated with
supplementary information
DOI: 10.1038/ncb2153 Figure S1 Ectopic expression of HAUSP up-regulates REST protein. (a) Immunoblotting showed that ectopic expression of HAUSP increased REST protein levels in ENStemA NPCs. (b) Immunofluorescent