DIALOG(R)File 159:Cancerlit　

(c) format only 1998 Dialog Corporation. All rts. reserv.　

　AN=,SF=

03869010 92052286 MEDL/92052286　

　/TI

  WILD-TYPE P53 CAN DOWN-MODULATE THE ACTIVITY OF VARIOUS PROMOTERS　

　AU=

    Ginsberg D; Mechta F; Yaniv M; Oren M　

　CS=

    Department of Chemical Immunology, Weizmann Institute of　

  Science, Rehovot, Israel.　

　JN=,PY=,SN=

    Proc Natl Acad Sci U S A; 88(22):9979-83 1991 ISSN 0027-8424　

　JC=

  Journal Code: PV3　

　CN=

    Contract/Grant No.: RO1 CA 40099　

　LA=

    Languages: ENGLISH　

　DT=

    Document Type: JOURNAL ARTICLE　

　JA=

    Journal Announcement: 9201　

　SF=

    Subfile: X; L; M　

　/AB

    The wild-type (wt) p53 protein is the product of a tumor suppres-　

sor gene that is a frequent target for inactivation in many types of　

tumors. The nuclear localization of the protein, as well as　

  additional features, suggest that it may be involved in the　

  regulation of gene expression. To explore this possibility,　

  the effects of overproduced wt p53 were investigated in a　

  number of systems. Induction of growth arrest via the antiprolif-　

  erative effect of wt p53 greatly impaired the ability of cells to　

  exhibit an increase in c-fos mRNA upon serum stimulation.　

  Experiments in which cells were cotransfected with p53 expression　

  plasmids together with a reporter gene linked to various　

  promoters revealed that wt p53 could effectively reduce　

  transcription from a series of promoters derived from serum-　

  inducible genes, but not from a major histocompatibility complex　

  gene. The p53-mediated repression of c-fos gene expression occurred　

  even in the presence of cycloheximide. Kinetic studies indicate　

  that the effect of wt p53 is rapid, rather than representing a　

  secondary consequence of growth arrest. These findings support　

  a role for p53 in transcriptional regulation, perhaps by　

  reducing the expression of genes that are needed for ongoing cell　

  proliferation.　

　/GS

    Tags: Animal; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.　

　/DE

   Major Descriptors: *Genes, fos; *Genes, p53; *Promoter Regions　

    (Genetics); *Protein p53--Genetics--GE　

    Minor Descriptors: Cells, Cultured; Chimera; Chloramphenicol　

Acetyltransferase--Genetics--GE; Chloramphenicol Acetyltransferase　

--Metabolism--ME; Cycloheximide--Pharmacology--PD; Kinetics; Mice;　

Plasmids ; Protein p53--Metabolism--ME; RNA, Messenger--Genetics　

--GE; Rats; Transcription, Genetic--Drug Effects--DE; Transfection　

　RN=,/ID

  CAS Registry No.: 66-81-9 (Cycloheximide)　

  Enzyme No.: EC 2.3.1.28 (Chloramphenicol Acetyltransferase)　

  Gene Symbol: c-fos