Modulation of mammalian life span by the short isoform of p53

被引:482
作者
Maier, B
Gluba, W
Bernier, B
Turner, T
Mohammad, K
Guise, T
Sutherland, A
Thorner, M
Scrable, H [1 ]
机构
[1] Univ Virginia, Sch Med, Dept Neurosci, Charlottesville, VA 22908 USA
[2] Univ Virginia, Sch Med, Dept Med, Charlottesville, VA 22908 USA
[3] Univ Virginia, Sch Med, Dept Urol, Charlottesville, VA 22908 USA
[4] Univ Virginia, Sch Med, Dept Cell Biol, Charlottesville, VA 22908 USA
关键词
daf2; GH; growth retardation; aging; testis; Akt; Sir2;
D O I
10.1101/gad.1162404
中图分类号
Q2 [细胞生物学];
学科分类号
071009 [细胞生物学]; 090102 [作物遗传育种];
摘要
Overexpression of the short isoform of p53 (p44) has unexpectedly uncovered a role for p53 in the regulation of size and life span in the mouse. Hyperactivation of the insulin-like growth factor (IGF) signaling axis by p44 sets in motion a kinase cascade that clamps potentially unimpeded growth through p21Cip1. This suggests that pathways of gene activity known to regulate longevity in lower organisms are linked in mammals via p53 to mechanisms for controlling cell proliferation. Thus, appropriate expression of the short and long p53 isoforms might maintain a balance between tumor suppression and tissue regeneration, a major requisite for long mammalian life span.
引用
收藏
页码:306 / 319
页数:14
相关论文
共 48 条
[1]
Reversal of human cellular senescence:: roles of the p53 and p16 pathways [J].
Beauséjour, CM ;
Krtolica, A ;
Galimi, F ;
Narita, M ;
Lowe, SW ;
Yaswen, P ;
Campisi, J .
EMBO JOURNAL, 2003, 22 (16) :4212-4222
[2]
BELLAMY GR, 1995, RURAL HLTH FOCUS, V6, P1
[3]
Extended longevity in mice lacking the insulin receptor in adipose tissue [J].
Blüher, M ;
Kahn, BB ;
Kahn, CR .
SCIENCE, 2003, 299 (5606) :572-574
[4]
Phosphorylation of human p53 by p38 kinase coordinates N-terminal phosphorylation and apoptosis in response to UV radiation [J].
Bulavin, DV ;
Saito, S ;
Hollander, MC ;
Sakaguchi, K ;
Anderson, CW ;
Appella, E ;
Fornace, AJ .
EMBO JOURNAL, 1999, 18 (23) :6845-6854
[5]
Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein [J].
Clancy, DJ ;
Gems, D ;
Harshman, LG ;
Oldham, S ;
Stocker, H ;
Hafen, E ;
Leevers, SJ ;
Partridge, L .
SCIENCE, 2001, 292 (5514) :104-106
[6]
ΔN-p53, a natural isoform of p53 lacking the first transactivation domain, counteracts growth suppression by wild-type p53 [J].
Courtois, S ;
Verhaegh, G ;
North, S ;
Luciani, MG ;
Lassus, P ;
Hibner, U ;
Oren, M ;
Hainaut, P .
ONCOGENE, 2002, 21 (44) :6722-6728
[7]
The lac operator-repressor system is functional in the mouse [J].
Cronin, CA ;
Gluba, W ;
Scrable, H .
GENES & DEVELOPMENT, 2001, 15 (12) :1506-1517
[8]
Caenorhabditis elegans p53:: Role in apoptosis, meiosis, and stress resistance [J].
Derry, WB ;
Putzke, AP ;
Rothman, JH .
SCIENCE, 2001, 294 (5542) :591-595
[9]
A BIOMARKER THAT IDENTIFIES SENESCENT HUMAN-CELLS IN CULTURE AND IN AGING SKIN IN-VIVO [J].
DIMRI, GP ;
LEE, XH ;
BASILE, G ;
ACOSTA, M ;
SCOTT, C ;
ROSKELLEY, C ;
MEDRANO, EE ;
LINSKENS, M ;
RUBELJ, I ;
PEREIRASMITH, O ;
PEACOCKE, M ;
CAMPISI, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (20) :9363-9367
[10]
Androgen deficiency induces high turnover osteopenia in aged male rats: A sequential histomorphometric study [J].
Erben, RG ;
Eberle, J ;
Stahr, K ;
Goldberg, M .
JOURNAL OF BONE AND MINERAL RESEARCH, 2000, 15 (06) :1085-1098