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| Regulation of p16(CDKN2) expression and its implications for cell immortalization and senescence |
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| Author(s): Hara E, Smith R, Parry D, Tahara H, Steven S, Peters G |
| Source: MOLECULAR AND CELLULAR BIOLOGY Volume: 16 Issue: 3 Pages: 859-867 Published: MAR 1996 |
| Times Cited: 462 References: 67 |
| Abstract: p16(CDKN2) specifically binds to and inhibits the cyclin-dependent kinases CDK4 and CDK6, which function as regulators of cell cycle progression in G(1) by contributing to the phosphorylation of the retinoblastoma protein (pRB). Human cell lines lacking functional pRB contain high levels of p16 RNA and protein, suggesting a negative feedback loop by which pRB might regulate p16 expression in late G(1). By a combination of nuclear run-on assays and promoter analyses in human fibroblasts expressing a temperature-sensitive simian virus 40 T antigen, we show that p16 transcription is affected by the status of pRB and define a region in the p16 promoter that is required for this response. However, the effect is not sufficient to account for the differences in p16 RNA levels between pRB-positive and -negative cells. Moreover, p16 RNA is extremely stable, and the levels do not change appreciably during the cell cycle. Primary human fibroblasts express very low levels of p16, but the RNA and protein accumulate in late-passage, senescent cells. The apparent overexpression of p16 in pRB-negative cell lines is therefore caused by at least two factors: loss of repression by pRB and an increase in the number of population doublings. |
| Document Type: Article |
| Language: English |
Addresses:
1. IMPERIAL CANC RES FUND, LONDON WC2A 3PX, ENGLAND
2. HIROSHIMA UNIV, SCH MED, HIROSHIMA 734, JAPAN
3. MYRIAD GENET INC, SALT LAKE CITY, UT 84108 USA |
| Publisher: AMER SOC MICROBIOLOGY, 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: TW172 |
| ISSN: 0270-7306 |
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