Inhibition of hTAFII32- binding implicated in the transcriptional repression by central regions of mutant p53 proteins.
We previously identified a movable and regulable inactivation function within the central region (CRts247) of a temperature-sensitive p53 (p53(ts)) mutant, p53(N247I). Here we showed that central regions from several p53(ts) mutants behaved similarly, i.e. they repressed a neighboring activation domain only when existing in the mutant status. Using chimeric protein GAL4VP16-CRts247 as an example, we demonstrated that de novo protein synthesis was not required for the reactivation of the chimeric protein, indicating that a post-translational mechanism was involved in the control of CRts247 activity. The CRts247-conferred thermo-regulability did not work via a mechanism demanding either an alteration of the subcellular compartmentalization of or the inactivation of DNA-binding activity of the GAL4 chimera. Further, CRts247 did not function in trans, eliminating the possibility that the observed repression was because of the competition for a putative factor(s) by the mutant p53 domain. Rather, CRts247 bestowed temperature-dependent interaction with hTAFII32 to the VP16 activation domain. In a parallel experiment, CRts247 also caused a large reduction in the affinity of hTAFII32 to the p53 activation domain at the nonpermissive temperature. These results strongly suggested that inhibition of hTAFII32 binding could be one of the mechanisms responsible for the transcriptional repression by mutant p53 central regions.[1]References
- Inhibition of hTAFII32-binding implicated in the transcriptional repression by central regions of mutant p53 proteins. Tung, S.F., Chuang, J.Y., Lin, C.T., Lai, M.Y., Wu, C.W., Lin, Y.S. J. Biol. Chem. (1999) [Pubmed]
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