p53 and a human premature ageing disorder

被引：6

作者：

O'Neill, M

Núñez, F

Melton, DW

机构：

[1] Univ Edinburgh, Western Gen Hosp, Mol Med Ctr, Sir Alastair Currie Canc Res UK Labs, Edinburgh EH4 2XU, Midlothian, Scotland

[2] Ctr Invest Canc, Salamanca 37007, Spain

来源：

MECHANISMS OF AGEING AND DEVELOPMENT | 2003年 / 124卷 / 05期

关键词：

progeria; p53; DNA damage; p21(WAF1); senescence;

D O I：

10.1016/S0047-6374(03)00007-1

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

It has been shown that enhanced levels of p53 activity contribute to reduced cancer susceptibility in mice, however longevity is compromised due to the onset of an early-ageing phenotype. The effects of enhanced levels of p53 in these in mice could therefore have implications for human premature ageing disorders. We examined the DNA damage response of p53 and its target p21(WAF1) to UV and ionising radiation in fibroblasts from patients with the premature ageing disorder Hutchinson-Gilford Progeria (HGP). We report a normal p53 response to these DNA damaging agents suggesting that, in this particular human disorder, the premature ageing phenotype does not arise from an enhanced p53 response. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

引用

页码：599 / 603

页数：5

共 14 条

[1] TELOMERE LENGTH PREDICTS REPLICATIVE CAPACITY OF HUMAN FIBROBLASTS [J].

ALLSOPP, RC ;

VAZIRI, H ;

PATTERSON, C ;

GOLDSTEIN, S ;

YOUNGLAI, EV ;

FUTCHER, AB ;

GREIDER, CW ;

HARLEY, CB .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (21) :10114-10118

[2]

Bentley DJ, 2002, J CELL SCI, V115, P1551

[3] Ageing - The price of tumour suppression? [J].

Ferbeyre, G ;

Lowe, SW .

NATURE, 2002, 415 (6867) :26-27

[4] 'Super p53' mice exhibit enhanced DNA damage response, are tumor resistant and age normally [J].

García-Cao, I ;

García-Cao, M ;

Martín-Caballero, J ;

Criado, LM ;

Klatt, P ;

Flores, JM ;

Weill, JC ;

Blasco, MA ;

Serrano, M .

EMBO JOURNAL, 2002, 21 (22) :6225-6235

[5] Progeria infantum (Hutchinson-Gilford syndrome) associated with scleroderma-like lesions and acro-osteolysis: A case report and brief review of the literature [J].

Jansen, T ;

Romiti, R .

PEDIATRIC DERMATOLOGY, 2000, 17 (04) :282-285

[6] Mitotic misregulation and human aging [J].

Ly, DH ;

Lockhart, DJ ;

Lerner, RA ;

Schultz, PG .

SCIENCE, 2000, 287 (5462) :2486-2492

[7] PRIMARY STRUCTURE POLYMORPHISM AT AMINO-ACID RESIDUE-72 OF HUMAN-P53 [J].

MATLASHEWSKI, GJ ;

TUCK, S ;

PIM, D ;

LAMB, P ;

SCHNEIDER, J ;

CRAWFORD, LV .

MOLECULAR AND CELLULAR BIOLOGY, 1987, 7 (02) :961-963

[8]

MIDGLEY CA, 1995, J CELL SCI, V108, P1843

[9]

Steele RJC, 1998, BRIT J SURG, V85, P1460

[10] Wild-type p53 triggers a rapid senescence program in human tumor cells lacking functional p53 [J].

Sugrue, MM ;

Shin, DY ;

Lee, SW ;

Aaronson, SA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (18) :9648-9653

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