p16 and ARF: activation of teenage proteins in old age.

The Journal of clinical investigation ·Vol. 114 ·No. 9 ·2004-11-00 ·Pages 1237-40

Satyanarayana A, Rudolph KL

Abstract

Cellular senescence induced by different stresses and telomere shortening appears to play an important role in the aging process. The products of the INK4a/ARF locus--p16INK4a and ARF--arrest cell proliferation at the senescence stage by exerting their effects on retinoblastoma protein- and p53-mediated responsive pathways. A study in this issue of the JCI provides experimental evidence of a specific upregulation of these cell cycle inhibitors in a variety of organs during mammalian aging.

MeSH Terms

ADP-Ribosylation Factor 1/physiology Aging Animals Biomarkers Cellular Senescence Cyclin-Dependent Kinase Inhibitor p16/physiology Gene Expression Regulation Humans Models, Biological Retinoblastoma Protein/metabolism Tumor Suppressor Protein p53/metabolism Up-Regulation

Chemicals

Biomarkers Cyclin-Dependent Kinase Inhibitor p16 Retinoblastoma Protein Tumor Suppressor Protein p53 ADP-Ribosylation Factor 1

Authors & Affiliations

2 authors, click to expand affiliations / ORCID

Satyanarayana Ande

Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany.

Rudolph K Lenhard

References (30)

30 references, click to expand

Insulin-like growth factor 1 (IGF-1) and aging: controversies and new insights.
Biogerontology. 2003;4(1):1-8 PMID: 12652183
Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts.
Mol Cell Biol. 1999 Mar;19(3):2109-17 PMID: 10022898
A DNA damage checkpoint response in telomere-initiated senescence.
Nature. 2003 Nov 13;426(6963):194-8 PMID: 14608368
Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks.
Nat Cell Biol. 2004 Feb;6(2):168-70 PMID: 14755273
Growth retardation and premature aging phenotypes in mice with disruption of the SNF2-like gene, PASG.
Genes Dev. 2004 May 1;18(9):1035-46 PMID: 15105378
Activation of the DNA damage response by telomere attrition: a passage to cellular senescence.
Cell Cycle. 2004 May;3(5):543-6 PMID: 15034298
Mitogen stimulation cooperates with telomere shortening to activate DNA damage responses and senescence signaling.
Mol Cell Biol. 2004 Jun;24(12):5459-74 PMID: 15169907
The biology of replicative senescence.
Eur J Cancer. 1997 Apr;33(5):703-9 PMID: 9282108
p16INK4A participates in a G1 arrest checkpoint in response to DNA damage.
Mol Cell Biol. 1998 Jan;18(1):378-87 PMID: 9418885
Molecular analysis of H2O2-induced senescent-like growth arrest in normal human fibroblasts: p53 and Rb control G1 arrest but not cell replication.
Biochem J. 1998 May 15;332 ( Pt 1):43-50 PMID: 9576849
Premature senescence involving p53 and p16 is activated in response to constitutive MEK/MAPK mitogenic signaling.
Genes Dev. 1998 Oct 1;12(19):3008-19 PMID: 9765203
Association of p19(ARF) with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53.
EMBO J. 1999 Jan 4;18(1):22-7 PMID: 9878046
The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus.
Nature. 1999 Jan 14;397(6715):164-8 PMID: 9923679
Is beta-galactosidase staining a marker of senescence in vitro and in vivo?
Exp Cell Res. 2000 May 25;257(1):162-71 PMID: 10854064
p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis.
Cell. 1999 May 14;97(4):527-38 PMID: 10338216
p16(INK4a) and the control of cellular proliferative life span.
Carcinogenesis. 1999 Jun;20(6):921-6 PMID: 10357768
CDK inhibitors: positive and negative regulators of G1-phase progression.
Genes Dev. 1999 Jun 15;13(12):1501-12 PMID: 10385618
Ink4a/Arf expression is a biomarker of aging.
J Clin Invest. 2004 Nov;114(9):1299-307 PMID: 15520862
Different telomere damage signaling pathways in human and mouse cells.
EMBO J. 2002 Aug 15;21(16):4338-48 PMID: 12169636
A senescence rescue screen identifies BCL6 as an inhibitor of anti-proliferative p19(ARF)-p53 signaling.
Genes Dev. 2002 Mar 15;16(6):681-6 PMID: 11914273
Oncogenic ras and p53 cooperate to induce cellular senescence.
Mol Cell Biol. 2002 May;22(10):3497-508 PMID: 11971980
E2F transcriptional repressor complexes are critical downstream targets of p19(ARF)/p53-induced proliferative arrest.
Cancer Cell. 2002 Jul;2(1):55-65 PMID: 12150825
p53: good cop/bad cop.
Cell. 2002 Jul 12;110(1):9-12 PMID: 12150992
"Super p53" mice exhibit enhanced DNA damage response, are tumor resistant and age normally.
EMBO J. 2002 Nov 15;21(22):6225-35 PMID: 12426394
Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence.
Nature. 2001 Feb 22;409(6823):1067-70 PMID: 11234019
Putative telomere-independent mechanisms of replicative aging reflect inadequate growth conditions.
Genes Dev. 2001 Feb 15;15(4):398-403 PMID: 11230148
p53 mutant mice that display early ageing-associated phenotypes.
Nature. 2002 Jan 3;415(6867):45-53 PMID: 11780111
Caloric restriction in primates.
Ann N Y Acad Sci. 2001 Apr;928:287-95 PMID: 11795520
Telomeres, aging and cancer: in search of a happy ending.
Oncogene. 2002 Jan 21;21(4):503-11 PMID: 11850775
Mitochondrial dysfunction leads to telomere attrition and genomic instability.
Aging Cell. 2002 Oct;1(1):40-6 PMID: 12882352

Article Info

Journal

The Journal of clinical investigation

Abbr.

J Clin Invest

ISSN

0021-9738

DOI

10.1172/JCI23437

Published

2004-11-00

Pages

1237-40

Language

English

Region

United States

NLM ID

7802877

PMCID

PMC524239

Subset

Corrections

CommentOn

PMID: 15520862

External Links

PubMed source DOI: 10.1172/JCI23437 PMC Full Text View journal details

Analysis Services

p16 and ARF: activation of teenage proteins in old age.

Contact

WeChat Official Account