PT  - JOURNAL ARTICLE
AU  - Yu, Hongyao
AU  - He, Ke
AU  - Wang, Lina
AU  - Hu, Jing
AU  - Gu, Junjie
AU  - Zhou, Chenlin
AU  - Lu, Rui
AU  - Jin, Ying
TI  - Stk40 represses adipogenesis through translational control of CCAAT/enhancer-binding proteins
AID  - 10.1242/jcs.170282
DP  - 2015 Aug 01
TA  - Journal of Cell Science
PG  - 2881--2890
VI  - 128
IP  - 15
4099  - http://jcs.biologists.org/content/128/15/2881.short
4100  - http://jcs.biologists.org/content/128/15/2881.full
SO  - J. Cell Sci.2015 Aug 01; 128
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) β and C/EBPδ, 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/EBPβ 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/EBPβ and C/EBPδ. 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.