Exit from G0 and entry into the cell cycle of cells expressing p21Sdi1 antisense RNA

Makoto Nakanishi, Guy R. Adami, Ryan S. Robetorye, Asao Noda, Susan F. Venable, Diana Dimitrov, Olivia M. Pereira-Smith, James R. Smith

Research output: Contribution to journalArticle

113 Scopus citations

Abstract

p21Sdi1 (also known as Cip1 and Waf1), an inhibitor of DNA synthesis cloned from senescent human fibroblasts, is an inhibitor of G1 cyclin-dependent kinases (Cdks) in vitro and is transcriptionally regulated by wild-type p53. In addition, p21Sdi1 has been found to inhibit DNA replication by direct interaction with proliferating cell nuclear antigen. In this study we analyzed normal human fibroblast cells arrested in G0 and determined that an excess of p21Sdi1 was present after immunodepletion of various cyclins and Cdks, in contrast to mitogen-stimulated cells in early S phase. Expression of antisense p21Sdi1 RNA in G0-arrested cells resulted in induction of DNA synthesis as well as entry into mitosis. These results suggest that p21Sdi1 functions in G0 and early G1 and that decreased expression of the gene is necessary for cell cycle progression.

Original languageEnglish (US)
Pages (from-to)4352-4356
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number10
DOIs
StatePublished - May 9 1995

Keywords

  • Cip1 protein
  • Waf1 protein

ASJC Scopus subject areas

  • General

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    Nakanishi, M., Adami, G. R., Robetorye, R. S., Noda, A., Venable, S. F., Dimitrov, D., Pereira-Smith, O. M., & Smith, J. R. (1995). Exit from G0 and entry into the cell cycle of cells expressing p21Sdi1 antisense RNA. Proceedings of the National Academy of Sciences of the United States of America, 92(10), 4352-4356. https://doi.org/10.1073/pnas.92.10.4352