Qq. Tang et Md. Lane, Role of C/EBP homologous protein (CHOP-10) in the programmed activation ofCCAAT/enhancer-binding protein-beta during adipogenesis, P NAS US, 97(23), 2000, pp. 12446-12450
Citations number
18
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Hormone induction of growth-arrested preadipocytes triggers mitotic clonal
expansion followed by expression of CCAAT/enhancer-binding protein (C/EBP)a
lpha and differentiation into adipocytes. The order of these events is crit
ical because C/EBP alpha is antimitotic and its expression prematurely woul
d block the mitotic: clonal expansion required for differentiation. C/EBP b
eta, a transcriptional activator of the C/EBP alpha gene, is expressed earl
y in the differentiation program. but lacks DNA-binding activity and fails
to localize to centromeres until preadipocytes traverse the G(1)-S checkpoi
nt of mitotic clonal expansion. Evidence is presented that dominant-negativ
e CHOP-10 expressed by growth-arrested preadipocytes transiently sequesters
C/EBP beta by heterodimerization. As preadipocytes reach S phase, CHOP-10
is down-regulated, apparently releasing C/EBP beta from inhibitory constrai
nt and allowing transactivation of the C/EBP alpha gene. In support of thes
e findings, up-regulation of CHOP-10 with the protease inhibitor N-acetyl-L
eu-Leu-norleucinal prevents activation of C/EBP beta. expression of C/EBP a
lpha, and adipogenesis.