The tumor suppression function of p21Waf is contained in its N-terminal half ('half-WAF').
The Waf-1 encoded protein, p21, mediates p53 suppression of tumor cell growth. Overexpression of p21 in the H1299 tumor cell line suppresses colony formation similar to that resulted from p53 overexpression. In an effort to localize the tumor suppression function within the structure of p21 we utilized vectors constructed with systematic truncations of p21 and tested their efficiency in suppressing tumor cell growth. We demonstrate that the N-terminal half of the p21 molecule (residues 1-80 and 1-89) shows better tumor cell growth suppression than the entire p21 molecule whereas the C-terminal half of p21 does not show this effect. These results may have implications for gene therapy of cancer.
Zakut
R
R
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Givol
D
D
D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000737:chemistry* / Q000235:genetics*; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000187:drug effects
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018076:DNA, Complementary; D010446:Peptide Fragments; D047428:Protein Kinase Inhibitors; D012097:Repressor Proteins