Abrogation of p27Kip1 by cDNA antisense suppresses quiescence (G0 state) in fibroblasts - PubMed (original) (raw)
. 1996 Aug 2;271(31):18337-41.
doi: 10.1074/jbc.271.31.18337.
Affiliations
- PMID: 8702474
- DOI: 10.1074/jbc.271.31.18337
Free article
Abrogation of p27Kip1 by cDNA antisense suppresses quiescence (G0 state) in fibroblasts
N Rivard et al. J Biol Chem. 1996.
Free article
Abstract
Progression of eukaryotic cells through the cell cycle is governed by the sequential formation, activation, and subsequent inactivation of a series of cyclin-dependent kinase (Cdk) complexes. p27(Kip1) (p27) is a Cdk inhibitor that blocks, in vitro, the activity of cyclin D-Cdk4, cyclin D-Cdk6, cyclin E-Cdk2 as well as cyclin A-Cdk2, a complex active during S phase. The level of p27 protein expression, usually high in G0/G1 resting cells, declines as cells progress toward S phase and enforced expression of p27 in fibroblasts causes G1 arrest. This situation prevails in CCL39, a Chinese hamster lung fibroblast cell line (this report). However, in addition to p27, several other Cdk inhibitors known to alter G1 progression coexist in most mammalian cells. To investigate the specific contribution of p27 in the control of the mitogen-sensitive G0/G1 arrest, we specifically reduced its synthesis by expressing a full-length p27 antisense cDNA in CCL39 cells. Interestingly, reduction of up to 90% of p27 protein expression increased both basal and serum-stimulated gene transcription of cyclin D1, cyclin A, dihydrofolate reductase, and DNA synthesis reinitiation. Moreover, overexpression of this antisense allows cells to grow for several generations in a serum-free medium supplemented with insulin and transferrin only, thus suggesting that p27-depleted cells cannot exit the cell cycle. These effects were fully reversed by coexpression of a plasmid encoding p27 sense. We conclude that p27, by setting the level of growth factor requirement, plays a pivotal role in controlling cell cycle exit, a fundamental step in growth control.
Similar articles
- Molecular mechanisms underlying interferon-alpha-induced G0/G1 arrest: CKI-mediated regulation of G1 Cdk-complexes and activation of pocket proteins.
Sangfelt O, Erickson S, Castro J, Heiden T, Gustafsson A, Einhorn S, Grandér D. Sangfelt O, et al. Oncogene. 1999 May 6;18(18):2798-810. doi: 10.1038/sj.onc.1202609. Oncogene. 1999. PMID: 10362250 - Cyclin D1 expression is a major target of the cAMP-induced inhibition of cell cycle entry in fibroblasts.
L'Allemain G, Lavoie JN, Rivard N, Baldin V, Pouyssegur J. L'Allemain G, et al. Oncogene. 1997 Apr 24;14(16):1981-90. doi: 10.1038/sj.onc.1201038. Oncogene. 1997. PMID: 9150365 - Formation of p27-CDK complexes during the human mitotic cell cycle.
Soos TJ, Kiyokawa H, Yan JS, Rubin MS, Giordano A, DeBlasio A, Bottega S, Wong B, Mendelsohn J, Koff A. Soos TJ, et al. Cell Growth Differ. 1996 Feb;7(2):135-46. Cell Growth Differ. 1996. PMID: 8822197 - [Molecular mechanisms controlling the cell cycle: fundamental aspects and implications for oncology].
Viallard JF, Lacombe F, Belloc F, Pellegrin JL, Reiffers J. Viallard JF, et al. Cancer Radiother. 2001 Apr;5(2):109-29. doi: 10.1016/s1278-3218(01)00087-7. Cancer Radiother. 2001. PMID: 11355576 Review. French. - Control of cell cycle transcription during G1 and S phases.
Bertoli C, Skotheim JM, de Bruin RA. Bertoli C, et al. Nat Rev Mol Cell Biol. 2013 Aug;14(8):518-28. doi: 10.1038/nrm3629. Nat Rev Mol Cell Biol. 2013. PMID: 23877564 Free PMC article. Review.
Cited by
- Unraveling the Big Sleep: Molecular Aspects of Stem Cell Dormancy and Hibernation.
Dias IB, Bouma HR, Henning RH. Dias IB, et al. Front Physiol. 2021 Apr 1;12:624950. doi: 10.3389/fphys.2021.624950. eCollection 2021. Front Physiol. 2021. PMID: 33867999 Free PMC article. Review. - Divide and conquer: two stem cell populations in squamous epithelia, reserves and the active duty forces.
Dunaway S, Rothaus A, Zhang Y, Luisa Kadekaro A, Andl T, Andl CD. Dunaway S, et al. Int J Oral Sci. 2019 Aug 27;11(3):26. doi: 10.1038/s41368-019-0061-2. Int J Oral Sci. 2019. PMID: 31451683 Free PMC article. Review. - Autophagy mediates serum starvation-induced quiescence in nucleus pulposus stem cells by the regulation of P27.
Li B, Sun C, Sun J, Yang MH, Zuo R, Liu C, Lan WR, Liu MH, Huang B, Zhou Y. Li B, et al. Stem Cell Res Ther. 2019 Apr 15;10(1):118. doi: 10.1186/s13287-019-1219-8. Stem Cell Res Ther. 2019. PMID: 30987681 Free PMC article. - LncRNA GAS5 regulates redox balance and dysregulates the cell cycle and apoptosis in malignant melanoma cells.
Chen L, Yang H, Yi Z, Jiang L, Li Y, Han Q, Yang Y, Zhang Q, Yang Z, Kuang Y, Zhu Y. Chen L, et al. J Cancer Res Clin Oncol. 2019 Mar;145(3):637-652. doi: 10.1007/s00432-018-2820-4. Epub 2018 Dec 19. J Cancer Res Clin Oncol. 2019. PMID: 30569211 Free PMC article. - Jab1 Silencing Inhibits Proliferation and Sensitizes to Cisplatin in Biliary Tract Cancer.
Nam AR, Kim JW, Park JE, Bang JH, Jin MH, Oh DY, Bang YJ. Nam AR, et al. Cancer Res Treat. 2019 Jul;51(3):886-900. doi: 10.4143/crt.2018.375. Epub 2018 Oct 1. Cancer Res Treat. 2019. PMID: 30282449 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous