p53 protein variants: structural and functional similarities with p63 and p73 isoforms

被引:84
作者
Courtois, S
de Fromentel, CC
Hainaut, P
机构
[1] Int Agcy Res Canc, Unit Mol Carcinogenesis, F-69372 Lyon 08, France
[2] Ctr Leon Berard, INSERM, U590, F-69373 Lyon 08, France
关键词
p53; family; isoform; regulation; alternative splicing; degradation;
D O I
10.1038/sj.onc.1206929
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Since its discovery in 1979, many studies have reported that the p53 tumour suppressor protein could be expressed in the form of products smaller than those predicted by the full-length amino-acid sequence. These products differ from full-length p53 in their N- or C-terminal regions, but generally conserve the central, DNA-binding domain. They appear to be expressed at rather low levels and to be restricted to particular cell types and/or physiological circumstances, suggesting that they play very narrow and specific roles. Several mechanisms have been proposed to explain their timely occurrence, including alternative splicing, internal initiation of translation or proteolytic cleavage. A precise assessment of the various 'p53 isoforms' reveals striking similarities with several isoforms of the p53 homologous proteins p63 or p73, suggesting that regulated production of specific, N- or C-terminal variants may be a 'trademark' of all family members. In this review, we summarize the published evidence on the structure, mode of production, expression and function of the p53 isoforms, and discuss their properties in the light of recent data on the structure and function of p63/p73 isoforms.
引用
收藏
页码:631 / 638
页数:8
相关论文
共 59 条
[1]   The C-terminus of p53: the more you learn the less you know [J].
Ahn, J ;
Prives, C .
NATURE STRUCTURAL BIOLOGY, 2001, 8 (09) :730-732
[2]   The murine C'-terminally alternatively spliced form of p53 induces attenuated apoptosis in myeloid cells [J].
Almog, N ;
Li, RZ ;
Peled, A ;
Schwartz, D ;
Wolkowicz, R ;
Goldfinger, N ;
Pei, HP ;
Rotter, V .
MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (02) :713-722
[3]   Reciprocal interference between the sequence-specific core and nonspecific C-terminal DNA binding domains of p53: Implications for regulation [J].
Anderson, ME ;
Woelker, B ;
Reed, M ;
Wang, P ;
Tegtmeyer, P .
MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (11) :6255-6264
[4]   IMMUNOLOGICALLY DISTINCT P53 MOLECULES GENERATED BY ALTERNATIVE SPLICING [J].
ARAI, N ;
NOMURA, D ;
YOKOTA, K ;
WOLF, D ;
BRILL, E ;
SHOHAT, O ;
ROTTER, V .
MOLECULAR AND CELLULAR BIOLOGY, 1986, 6 (09) :3232-3239
[5]   Latent and active p53 are identical in conformation [J].
Ayed, A ;
Mulder, FAA ;
Yi, GS ;
Lu, Y ;
Kay, LE ;
Arrowsmith, CH .
NATURE STRUCTURAL BIOLOGY, 2001, 8 (09) :756-760
[6]   Alternative initiation of translation accounts for a 67/45 kDa dimorphism of the human estrogen receptor ERα [J].
Barraille, P ;
Chinestra, P ;
Bayard, F ;
Faye, JC .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 257 (01) :84-88
[7]   THE CARBOXYL-TERMINAL DOMAIN OF THE P53 PROTEIN REGULATES SEQUENCE-SPECIFIC DNA-BINDING THROUGH ITS NONSPECIFIC NUCLEIC ACID-BINDING ACTIVITY [J].
BAYLE, JH ;
ELENBAAS, B ;
LEVINE, AJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (12) :5729-5733
[8]   Alternate choice of initiation codon produces a biologically active product of the von Hippel Lindau gene with tumor suppressor activity [J].
Blankenship, C ;
Naglich, JG ;
Whaley, JM ;
Seizinger, B ;
Kley, N .
ONCOGENE, 1999, 18 (08) :1529-1535
[9]  
BRAIN R, 1994, ONCOGENE, V9, P1775
[10]   Two tandem and independent sub-activation domains in the amino terminus of p53 require the adaptor complex for activity [J].
Candau, R ;
Scolnick, DM ;
Darpino, P ;
Ying, CY ;
Halazonetis, TD ;
Berger, SL .
ONCOGENE, 1997, 15 (07) :807-816