NDLI: Map4k4 Negatively Regulates Peroxisome Proliferator-activated Receptor (PPAR) γ Protein Translation by Suppressing the Mammalian Target of Rapamycin (mTOR) Signaling Pathway in Cultured Adipocytes*

Content Provider	PubMed Central
Author	Guntur, Kalyani V. P. Guilherme, Adilson Xue, Liting Chawla, Anil Czech, Michael P.
Abstract	The receptor peroxisome proliferator-activated receptor γ (PPARγ) is considered a master regulator of adipocyte differentiation and promotes glucose and lipid metabolism in mature adipocytes. We recently identified the yeast Sterile 20 (Ste20) protein kinase ortholog, Map4k4, in an RNA interference-based screen as an inhibitor of PPARγ expression in cultured adipocytes. Here, we show that RNA interference-mediated silencing of Map4k4 elevates the levels of both PPARγ1 and PPARγ2 proteins in 3T3-L1 adipocytes without affecting PPARγ mRNA levels, suggesting that Map4k4 regulates PPARγ at a post-transcriptional step. PPARγ degradation rates are remarkably rapid as measured in the presence of cycloheximide (t ½ = 2 h), but silencing Map4k4 had no effect on PPARγ degradation. However, depletion of Map4k4 significantly enhances [35S]methionine/cysteine incorporation into proteins, suggesting that Map4k4 signaling decreases protein translation. We show a function of Map4k4 is to inhibit rapamycin-sensitive mammalian target of rapamycin (mTOR) activity, decreasing 4E-BP1 phosphorylation. In addition, our results show mTOR and 4E-BP1 are required for the increased PPARγ protein expression upon Map4k4 knockdown. Consistent with this concept, adenovirus-mediated expression of Map4k4 decreased PPARγ protein levels and mTOR phosphorylation. These data show that Map4k4 negatively regulates PPARγ post-transcriptionally, by attenuating mTOR signaling and a 4E-BP1-dependent mechanism.
Related Links	http://dx.doi.org/10.1074/jbc.m109.068502
Ending Page	6603
Page Count	9
Starting Page	6595
File Format	PDF
ISSN	00219258
e-ISSN	1083351X
Journal	The Journal of Biological Chemistry
Issue Number	9
Volume Number	285
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2010-02-26
Access Restriction	Open
Rights Holder	American Society for Biochemistry and Molecular Biology
Subject Keyword	Cell Biology Biochemistry Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Map4k4 Negatively Regulates Peroxisome Proliferator-activated Receptor (PPAR) γ Protein Translation by Suppressing the Mammalian Target of Rapamycin (mTOR) Signaling Pathway in Cultured Adipocytes

Regulation of Peroxisome Proliferator–Activated Receptor-γ Activity by Mammalian Target of Rapamycin and Amino Acids in Adipogenesis

G Protein-coupled Receptor 40 (GPR40) and Peroxisome Proliferator-activated Receptor γ (PPARγ) AN INTEGRATED TWO-RECEPTOR SIGNALING PATHWAY

Relaxin Activates Peroxisome Proliferator-activated Receptor γ (PPARγ) through a Pathway Involving PPARγ Coactivator 1α (PGC1α)

Fam57b (Family with Sequence Similarity 57, Member B), a Novel Peroxisome Proliferator-activated Receptor γ Target Gene That Regulates Adipogenesis through Ceramide Synthesis

Chrysophanol Suppresses Cell Growth via mTOR/PPAR-α Regulation and ROS Accumulation in Cultured Human Tongue Squamous Carcinoma SAS Cells

Peroxisome proliferator-activated receptor-γ agonist inhibits the mammalian target of rapamycin signaling pathway and has a protective effect in a rat model of status epilepticus

Thioredoxin-Binding Protein-2-Like Inducible Membrane Protein Is a Novel Vitamin D3 and Peroxisome Proliferator-Activated Receptor (PPAR)γ Ligand Target Protein that Regulates PPARγ Signaling

Reactive Oxygen Species (ROS) Mediate p300-dependent STAT1 Protein Interaction with Peroxisome Proliferator-activated Receptor (PPAR)-γ in CD36 Protein Expression and Foam Cell Formation

Map4k4 Negatively Regulates Peroxisome Proliferator-activated Receptor (PPAR) γ Protein Translation by Suppressing the Mammalian Target of Rapamycin (mTOR) Signaling Pathway in Cultured Adipocytes*

Similar Documents

Map4k4 Negatively Regulates Peroxisome Proliferator-activated Receptor (PPAR) γ Protein Translation by Suppressing the Mammalian Target of Rapamycin (mTOR) Signaling Pathway in Cultured Adipocytes

Regulation of Peroxisome Proliferator–Activated Receptor-γ Activity by Mammalian Target of Rapamycin and Amino Acids in Adipogenesis

G Protein-coupled Receptor 40 (GPR40) and Peroxisome Proliferator-activated Receptor γ (PPARγ) AN INTEGRATED TWO-RECEPTOR SIGNALING PATHWAY

Relaxin Activates Peroxisome Proliferator-activated Receptor γ (PPARγ) through a Pathway Involving PPARγ Coactivator 1α (PGC1α)

Fam57b (Family with Sequence Similarity 57, Member B), a Novel Peroxisome Proliferator-activated Receptor γ Target Gene That Regulates Adipogenesis through Ceramide Synthesis

Chrysophanol Suppresses Cell Growth via mTOR/PPAR-α Regulation and ROS Accumulation in Cultured Human Tongue Squamous Carcinoma SAS Cells

Peroxisome proliferator-activated receptor-γ agonist inhibits the mammalian target of rapamycin signaling pathway and has a protective effect in a rat model of status epilepticus

Thioredoxin-Binding Protein-2-Like Inducible Membrane Protein Is a Novel Vitamin D3 and Peroxisome Proliferator-Activated Receptor (PPAR)γ Ligand Target Protein that Regulates PPARγ Signaling

Reactive Oxygen Species (ROS) Mediate p300-dependent STAT1 Protein Interaction with Peroxisome Proliferator-activated Receptor (PPAR)-γ in CD36 Protein Expression and Foam Cell Formation

Map4k4 Negatively Regulates Peroxisome Proliferator-activated Receptor (PPAR) γ Protein Translation by Suppressing the Mammalian Target of Rapamycin (mTOR) Signaling Pathway in Cultured Adipocytes*