NDLI: CCAAT / enhancer-binding protein ( C / EBP ) inhibits cell proliferation through the p 21 ( WAF-1 / CIP-1 / SDI-1 ) protein

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CCAAT / enhancer-binding protein ( C / EBP ) inhibits cell proliferation through the p 21 ( WAF-1 / CIP-1 / SDI-1 ) protein

Content Provider	Semantic Scholar
Author	Imchenko, Nikolai A. T. Wilde, Margie Nakanishi, Makoto Smith, James R. Darlington, Gretchen J.
Copyright Year	2007
Abstract	C/EBPc~ has a role in growth arrest and differentiation of mouse preadipocytes. To study the mechanism of C/EBP,v-induced growth arrest, we developed a cell line, HT1, that contained the human C/EBP~ gene under Lac repressor control. IPTG-induced C/EBPc~ caused inhibition of cell proliferation and DNA synthesis as measured by colony growth assays, cell counting, and BrdU uptake. A number of proteins that are known to be involved in the regulation of the cell cycle, such as cyclin-dependent kinase (CDK) 2 and CDK4, proliferating cell nuclear antigen (PCNA), p53, c-fos, and the CDK inhibitor p16 and p27 were investigated by Western analysis. No change in their expression was observed. However, the p21 (WAF-1/CIP-1 / SDI-1) protein was significantly elevated in growth-arrested HT1 cells. Elevation of p21/SDI-1 mRNA (threefold) and activation of the p21/SDI-1 promoter by C/EBPot did not account for the 12to 20-fold increase in p21/SDI-1 protein. Protein synthesis inhibition by cycloheximide (CHX) treatment indicated that the half-life of p21/SDI-1 in dividing HT1 cells was 3 0 min. However, in C/EBP,~ growth-arrested cells, the level of the p21/SDI-1 did not change for >80 rain after CHX addition. Our studies demonstrate that C/EBPa activates p21/SDI-1 by increasing p21/SDI-1 gene expression and by post-translational stabilization of p21/SDI-1 protein. Furthermore, induction of p21/SDI-1 is responsible for the ability of C/EBP,v to inhibit proliferation because transcription of antisense p21/SDI-1 mRNA eliminated growth inhibition by C/EBPa.
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://genesdev.cshlp.org/content/10/7/804.full.pdf
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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