Modifications of p53 protein and accumulation of p21 and gadd45 mRNA in TGF-beta 1 growth inhibited cells

被引:27
作者
Landesman, Y
Bringold, F
Milne, DD
Meek, DW
机构
[1] WEIZMANN INST SCI, DEPT MOL GENET & VIROL, IL-76100 REHOVOT, ISRAEL
[2] GERMAN CANC RES CTR, DIV DIFFERENTIAT & CARCINOGENESIS INVITRO, D-69120 HEIDELBERG, GERMANY
[3] UNIV DUNDEE, NINEWELLS HOSP & MED SCH, CTR BIOMED RES, DUNDEE DD1 9SY, SCOTLAND
关键词
transforming growth factor beta 1; growth inhibition; p53; p21; gadd45; cdk site of phosphorylation; nuclear localization;
D O I
10.1016/S0898-6568(97)89890-7
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Transforming growth factory beta (TGF-beta) is a potent growth inhibitor of epithelial cells. One of the strategies used to elucidate the anti-proliferative mode of action of TGF-beta is to find out whether the receptor-generated signals interact with components of the basic machinery of the cell cycle. In this study we examined whether p53 and two other cell cycle inhibitory genes that can be transactivated by p53 are affected by TGF-beta 1 in epithelial cells. We show that TGF-beta 1 signalling controls the intracellular localization as well as the phosphorylation pattern and the stability of p53 protein. TGF-beta signalling also elevates the expression of p21/waf-1 and gadd45. The observed modifications in the protein suggest that p53 is involved in mediation of TGF-beta 1 growth inhibition. However, in TGF-beta 1 growth inhibited cells, wild type p53 is not required for the accumulation of the two p53 downstream targets p21/waf-1 and gadd45. (C) 1997 Elsevier Science Inc.
引用
收藏
页码:291 / 298
页数:8
相关论文
共 47 条
  • [41] NUCLEAR ACCUMULATION OF P53 PROTEIN IS MEDIATED BY SEVERAL NUCLEAR-LOCALIZATION SIGNALS AND PLAYS A ROLE IN TUMORIGENESIS
    SHAULSKY, G
    GOLDFINGER, N
    BENZEEV, A
    ROTTER, V
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1990, 10 (12) : 6565 - 6577
  • [42] STURZBECHER HW, 1990, ONCOGENE, V5, P795
  • [43] P27, A NOVEL INHIBITOR OF G1 CYCLIN-CDK PROTEIN-KINASE ACTIVITY, IS RELATED TO P21
    TOYOSHIMA, H
    HUNTER, T
    [J]. CELL, 1994, 78 (01) : 67 - 74
  • [44] INCREASED AND ALTERED DNA-BINDING OF HUMAN P53 BY S AND G2/M BUT NOT G1 CYCLIN-DEPENDENT KINASES
    WANG, Y
    PRIVES, C
    [J]. NATURE, 1995, 376 (6535) : 88 - 91
  • [45] MONOCLONAL-ANTIBODY ANALYSIS OF P53 EXPRESSION IN NORMAL AND TRANSFORMED-CELLS
    YEWDELL, JW
    GANNON, JV
    LANE, DP
    [J]. JOURNAL OF VIROLOGY, 1986, 59 (02) : 444 - 452
  • [46] WILD-TYPE P53 INDUCES APOPTOSIS OF MYELOID LEUKEMIC-CELLS THAT IS INHIBITED BY INTERLEUKIN-6
    YONISHROUACH, E
    RESNITZKY, D
    LOTEM, J
    SACHS, L
    KIMCHI, A
    OREN, M
    [J]. NATURE, 1991, 352 (6333) : 345 - 347
  • [47] EARLY GENE RESPONSES TO TRANSFORMING GROWTH-FACTOR-BETA IN CELLS LACKING GROWTH-SUPPRESSIVE RB FUNCTION
    ZENTELLA, A
    WEIS, FMB
    RALPH, DA
    LAIHO, M
    MASSAGUE, J
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1991, 11 (10) : 4952 - 4958