Gas1-induced growth suppression requires a transactivation-independent p53 function.
In normal cells, induction of quiescence is accompanied by the increased expression of growth arrest-specific genes (gas). One of them, gas1, is regulated at the transcriptional level and codes for a membrane-associated protein (Gas1) which is down regulated during the G0-to-S phase transition in serum-stimulated cells. Gas1 is not expressed in growing or transformed cells, and when overexpressed in normal fibroblasts, it blocks the G0-to-S phase transition. Moreover, Gas1 blocks cell proliferation in several transformed cells with the exception of simian virus 40- or adenovirus-transformed cell lines. In this paper, we demonstrate that overexpression of Gas1 blocks cell proliferation in a p53-dependent manner and that the N-terminal domain-dependent transactivating function of p53 is dispensable for Gas1-induced growth arrest. These data therefore indicate that the other intrinsic transactivation-independent functions of p53, possibly related to regulation of apoptosis, should be involved in mediating Gas1-induced growth arrest.
Laboratorio Nazionale Consorzio Interuniversitario per le Biotecnologie, Trieste, Italy.
G
G
Del Sal
E M
EM
Ruaro
R
R
Utrera
C N
CN
Cole
A J
AJ
Levine
C
C
Schneider
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D001483:Base Sequence; D015153:Blotting, Western; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000502:physiology*; D002461:Cell Line, Transformed; D015500:Chloramphenicol O-Acetyltransferase / Q000032:analysis / Q000096:biosynthesis; D017931:DNA Primers; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation; D008565:Membrane Proteins / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis; D016192:Resting Phase, Cell Cycle; D016196:S Phase; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000906:Antibodies; D018797:Cell Cycle Proteins; D017931:DNA Primers; C096192:GAS1 protein, human; D058851:GPI-Linked Proteins; C501180:Gas1 protein, mouse; D008565:Membrane Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D015500:Chloramphenicol O-Acetyltransferase