The basic carboxy-terminal domain of human p53 is dispensable for both transcriptional regulation and inhibition of tumor cell growth.

摘要: Abstract To investigate the relevance of C-terminal domains human p53 tumor suppressor gene to its growth suppressive and transcriptional regulatory properties deletion mutants were generated which eliminated 30 (p53 delta 363), 60 333) 87 306) amino acids from C-terminus protein. 363 has lost highly basic tail protein (residues 360-386). 333 306 lack oligomerization domain 320-360); also major nuclear localization signal (NLSI, residues 316-325). These assayed for transactivation two consensus binding sites repression promoter systems in Calu6 lung cancer cells null). Moreover, their ability inhibit cell lines with a defined status was analysed. Deletion correlated significant loss of: (a) genomic sequence; (b) repression; (c) colony formation. An intact NLSI not prerequisite transactivation. behaved similarly wt all assays. We established an inducible expression system fibrosarcoma line known be growth-suppressed by p53. The induction inhibited proliferation albeit lesser extent than However, could upregulate WAF1/CIP1, GADD45 MDM2 genes. Thus, basis appears required biological functions assayed.