PMID: 8943005Nov 26, 1996Paper

Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts

Proceedings of the National Academy of Sciences of the United States of America
D A AlcortaJ C Barrett

Abstract

Human diploid fibroblasts (HDFs) can be grown in culture for a finite number of population doublings before they cease proliferation and enter a growth-arrest state termed replicative senescence. The retinoblastoma gene product, Rb, expressed in these cells is hypophosphorylated. To determine a possible mechanism by which senescent human fibroblasts maintain a hypophosphorylated Rb, we examined the expression levels and interaction of the Rb kinases, CDK4 and CDK6, and the cyclin-dependent kinase inhibitors p21 and p16 in senescent HDFs. Cellular p21 protein expression increased dramatically during the final two to three passages when the majority of cells lost their growth potential and neared senescence but p21 levels declined in senescent HDFs. During this period, p16 mRNA and cellular protein levels gradually rose with the protein levels in senescent HDFs reaching nearly 40-fold higher than early passage cells. In senescent HDFs, p16 was shown to be complexed to both CDK4 and CDK6. Immunodepletion analysis of p21 and p16 from the senescent cell extracts revealed that p16 is the major CDK inhibitor for both CDK4 and CDK6 kinases. Immunoprecipitation of CDK4 and CDK6 and their associated proteins from radiolabeled extracts fr...Continue Reading

References

Jul 1, 1992·Experimental Gerontology·V J CristofaloM O Rotenberg
Sep 1, 1991·Experimental Cell Research·J W ShayW E Wright
Oct 12, 1995·Nature·J BrugarolasG J Hannon
May 15, 1995·Genes & Development·C J Sherr, J M Roberts
Nov 19, 1993·Cell·W S el-DeiryB Vogelstein
Dec 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·V DulićG H Stein
Dec 16, 1993·Nature·Y XiongD Beach
Jul 1, 1993·Physiological Reviews·V J Cristofalo, R J Pignolo
Jul 26, 1996·Cell·M M Zambrano, R Kolter
Jul 26, 1996·Cell·G TianN J Cowan
Jan 1, 1996·Experimental Gerontology·H Wong, K Riabowol
Aug 1, 1996·Molecular Carcinogenesis·L A TerryJ C Barrett
Mar 1, 1965·Experimental Cell Research·L HAYFLICK

❮ Previous
Next ❯

Citations

Mar 19, 1999·Journal of Cellular Physiology·K SayamaK Hashimoto
Feb 27, 1999·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·R R Reddel
Aug 10, 1999·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·M V Blagosklonny
Jan 25, 2002·Journal of Cellular Physiology·Yoshifumi Yokota, Seiichi Mori
Mar 27, 2001·Journal of Cellular Physiology·K WheatonK Riabowol
Apr 5, 2001·Journal of Biomedical Science·Z F Chang, D Y Huang
Jun 10, 2011·Archives of Dermatological Research·Young Mee LeeJin Ho Chung
Sep 19, 2009·Pflügers Archiv : European journal of physiology·Peter J Hornsby
Jul 18, 2009·Biogerontology·Alvaro Macieira-Coelho
Feb 26, 2004·Free Radical Biology & Medicine·Mei-Ling ChengDaniel Tsun-Yee Chiu
May 8, 2004·Mechanisms of Ageing and Development·Ji Hyun HanJin Ho Chung
May 4, 2000·The American Journal of Pathology·D G FarwellA J Klingelhutz
Dec 10, 2002·Mechanisms of Ageing and Development·Eun Seong Hwang
Oct 24, 2002·Human Immunology·Urban J ScheuringArgyrios N Theofilopoulos
Nov 21, 1998·Biochimica Et Biophysica Acta·M Ruas, G Peters
Jun 1, 2000·Experimental Gerontology·F Bringold, M Serrano
Sep 9, 2000·Experimental Gerontology·E J YeoS C Park
Oct 8, 1998·Experimental Gerontology·H Kitano, S Imai
Nov 7, 2000·Current Opinion in Cell Biology·A S LundbergR A Weinberg
Jun 26, 1998·Current Opinion in Cell Biology·F B JohnsonL Guarente
Aug 15, 2002·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·N ZaffaroniM G Daidone

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.