PMID- 26065429
OWN - NLM
STAT- MEDLINE
DCOM- 20160614
LR  - 20211203
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Linking)
VI  - 128
IP  - 15
DP  - 2015 Aug 1
TI  - Stk40 represses adipogenesis through translational control of 
      CCAAT/enhancer-binding proteins.
PG  - 2881-90
LID - 10.1242/jcs.170282 [doi]
AB  - A better understanding of molecular regulation in adipogenesis might help the 
      development of efficient strategies to cope with obesity-related diseases. Here, 
      we report that CCAAT/enhancer-binding protein (C/EBP) beta and C/EBPdelta, two crucial 
      pro-adipogenic transcription factors, are controlled at a translational level by 
      serine/threonine kinase 40 (Stk40). Genetic knockout (KO) or knockdown (KD) of 
      Stk40 leads to increased protein levels of C/EBP proteins and adipocyte 
      differentiation in mouse embryonic fibroblasts (MEFs), fetal liver stromal cells, 
      and mesenchymal stem cells (MSCs). In contrast, overexpression of Stk40 abolishes 
      the enhanced C/EBP protein translation and adipogenesis observed in Stk40-KO and 
      -KD cells. Functionally, knockdown of C/EBPbeta eliminates the enhanced adipogenic 
      differentiation in Stk40-KO and -KD cells substantially. Mechanistically, 
      deletion of Stk40 enhances phosphorylation of eIF4E-binding protein 1, leading to 
      increased eIF4E-dependent translation of C/EBPbeta and C/EBPdelta. Knockdown of eIF4E in 
      MSCs decreases translation of C/EBP proteins. Moreover, Stk40-KO fetal livers 
      display an increased adipogenic program and aberrant lipid and steroid 
      metabolism. Collectively, our study uncovers a new repressor of C/EBP protein 
      translation as well as adipogenesis and provides new insights into the molecular 
      mechanism underpinning the adipogenic program.
CI  - (c) 2015. Published by The Company of Biologists Ltd.
FAU - Yu, Hongyao
AU  - Yu H
AD  - Laboratory of Molecular Developmental Biology, Shanghai Jiao Tong University 
      School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
FAU - He, Ke
AU  - He K
AD  - Laboratory of Molecular Developmental Biology, Shanghai Jiao Tong University 
      School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
FAU - Wang, Lina
AU  - Wang L
AD  - Laboratory of Molecular Developmental Biology, Shanghai Jiao Tong University 
      School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
FAU - Hu, Jing
AU  - Hu J
AD  - Laboratory of Molecular Developmental Biology, Shanghai Jiao Tong University 
      School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
FAU - Gu, Junjie
AU  - Gu J
AD  - Laboratory of Molecular Developmental Biology, Shanghai Jiao Tong University 
      School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
FAU - Zhou, Chenlin
AU  - Zhou C
AD  - Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai 
      Institute for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, 
      Shanghai 200031, China.
FAU - Lu, Rui
AU  - Lu R
AD  - Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai 
      Institute for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, 
      Shanghai 200031, China.
FAU - Jin, Ying
AU  - Jin Y
AD  - Laboratory of Molecular Developmental Biology, Shanghai Jiao Tong University 
      School of Medicine, 280 South Chongqing Road, Shanghai 200025, China Key 
      Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institute 
      for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 
      200031, China yjin@sibs.ac.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150611
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (CCAAT-Enhancer-Binding Protein-beta)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Eif4ebp1 protein, mouse)
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - 0 (Eukaryotic Initiation Factors)
RN  - 0 (Phosphoproteins)
RN  - 0 (eIF4E protein, mouse)
RN  - 142662-43-9 (CCAAT-Enhancer-Binding Protein-delta)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Stk40 protein, mouse)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adaptor Proteins, Signal Transducing
MH  - Adipogenesis/*genetics
MH  - Animals
MH  - CCAAT-Enhancer-Binding Protein-beta/*genetics
MH  - CCAAT-Enhancer-Binding Protein-delta/*genetics
MH  - Carrier Proteins/metabolism
MH  - Cell Cycle Proteins
MH  - Cell Line
MH  - Eukaryotic Initiation Factor-4E/genetics
MH  - Eukaryotic Initiation Factors
MH  - Gene Knockout Techniques
MH  - Lipid Metabolism/genetics
MH  - Mice
MH  - Obesity/genetics
MH  - Phosphoproteins/metabolism
MH  - Promoter Regions, Genetic
MH  - Protein Binding/genetics
MH  - Protein Biosynthesis/genetics
MH  - Protein Serine-Threonine Kinases/*genetics/metabolism
OTO - NOTNLM
OT  - 4E-BP1
OT  - Adipogenesis
OT  - C/EBP
OT  - Stk40
OT  - eIF4E
EDAT- 2015/06/13 06:00
MHDA- 2016/06/15 06:00
CRDT- 2015/06/13 06:00
PHST- 2015/02/15 00:00 [received]
PHST- 2015/06/04 00:00 [accepted]
PHST- 2015/06/13 06:00 [entrez]
PHST- 2015/06/13 06:00 [pubmed]
PHST- 2016/06/15 06:00 [medline]
AID - jcs.170282 [pii]
AID - 10.1242/jcs.170282 [doi]
PST - ppublish
SO  - J Cell Sci. 2015 Aug 1;128(15):2881-90. doi: 10.1242/jcs.170282. Epub 2015 Jun 
      11.