Regulation of p16CDKN2 Expression and Its Implications for Cell Immortalization and Senescence

• DOI: 10.1128/mcb.16.3.859
• Publication Date: 2015-10-09T00:22:49Z
• Authors: Eiji Hara; Rosalind Smith; David Parry; Hidetoshi Tahara; Steven Stone; Gordon Peters
• Keywords: Senescence; Expression (computer science); Cellular senescence

p16CDKN2 specifically binds to and inhibits the cyclin-dependent kinases CDK4 CDK6, which function as regulators of cell cycle progression in G1 by contributing phosphorylation retinoblastoma protein (pRB). Human lines lacking functional pRB contain high levels p16 RNA protein, suggesting a negative feedback loop might regulate expression late G1. By combination nuclear run-on assays promoter analyses human fibroblasts expressing temperature-sensitive simian virus 40 T antigen, we show that transcription is affected status define region required for this response. However, effect not sufficient account differences between pRB-positive -negative cells. Moreover, extremely stable, do change appreciably during cycle. Primary express very low p16, but accumulate late-passage, senescent The apparent overexpression pRB-negative therefore caused at least two factors: loss repression an increase number population doublings.