Effect of prothymosin alpha and its mutants on the activity of the p53 tumor suppressorстатья
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 18 июля 2013 г.
Аннотация:The nuclear oncoprotein prothymosin alpha (ProT alpha) was tested for the ability to regulate the p53 activity with the use of a reporter gene controlled by a p53-responsive promoter. Overexpression of the ProT alpha gene stimulated the p53 activity, while downregulation of the endogenous ProT alpha level via RNA interference suppressed transcription of the reporter gene. An increase in ProT alpha activated p53-dependent transcription and increased the intracellular p53 content in human HeLa, but not HCT116, cells. N-terminal deletions had almost no effect on the ability of ProT alpha to activate p53-dependent transcription, while deletions from the central region and C-terminal mutations distorting the active transport of ProT alpha into the cell nucleus prevented its transactivating effect. Mutations affecting Keap1 binding did not impair the ProT alpha ability to activate the p53-responsive reporter gene. Based on the results, stimulation of p53-dependent transcription was ascribed to the central acidic region of ProT alpha. The conclusion was supported by the fact that parathymosin, another protein containing an extended acidic region, was also capable of activating p53.