Effect of serum on the down-regulation of CHOP-10 during differentiation of 3T3-L1 preadipocytes.
Hormonal induction of growth-arrested 3T3-L1 preadipocytes in medium containing fetal bovine serum (FBS) triggers a signaling cascade that culminates in adipogenesis. The transcription factor, C/EBPbeta, is expressed early in this differentiation program, but lacks DNA-binding activity until much later as the preadipocytes traverse the G(1)-S checkpoint of mitotic clonal expansion. Dominant-negative CHOP-10 is initially expressed by growth-arrested preadipocytes and sequesters/inactivates C/EBPbeta by heterodimerization with its leucine zipper. After a lag period, CHOP-10 undergoes down-regulation releasing C/EBPbeta from inhibitory constraint allowing transactivation of the C/EBPalpha and PPARgamma genes, transcription factors required for terminal differentiation. We verify that following induction of differentiation in FBS-containing medium, CHOP-10 undergoes down-regulation and differentiation occurs normally. However, when differentiation is induced in calf serum-containing medium, CHOP-10 is not down-regulated resulting in delayed and incomplete differentiation. Under these conditions the expression of C/EBPalpha and PPARgamma and the accumulation of cytoplasmic triglyceride are attenuated. It appears that a factor(s) present in FBS is required to affect the down-regulation of CHOP-10 necessary for successful terminal differentiation.
Huang
Haiyan
H
Key Laboratory of Molecular Medicine, Ministry of Education, Fu Dan University, Shanghai 200032, People's Republic of China.
Lane
M Daniel
MD
Tang
Qi-Qun
QQ
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D015536:Down-Regulation; D051379:Mice; D044967:Serum / Q000378:metabolism*; D051742:Transcription Factor CHOP / Q000378:metabolism*
C497250:Ddit3 protein, mouse; D051742:Transcription Factor CHOP