[Influence of prothymosin alpha and its mutants on activity of the p53 tumor suppressor].
Overexpression of the nuclear oncoprotein prothymosin a enhanced and, in a reciprocal experiment, down-regulation of endogenous prothymosin alpha by RNA interference approach inhibited transcriptional activity of the p53 tumor suppressor in the reporter gene assay. Ectopic expression of prothymosin alpha enhanced not only p53-dependent transcription, but also intracellular level of p53 in HeLa (but not HCT116) cells. Ability to stimulate p53-dependent transcription was lost by C-terminal mutants of prothymosin alpha with impaired nuclear accumulation, but not by N-terminal deletion mutants and by the double mutant of prothymosin alpha with impaired ability to bind Keap1, suggesting that prothymosinalpha-Keap1 interaction is dispensable for p53 response. Our data suggest that the central "acidic" region of prothymosin alpha together with intact nuclear localization signal is responsible for stimulation of p53-dependent transcription. This conclusion was confirmed by the fact that another protein containing long "acidic" region and nuclear localization signal, parathymosin, was able to stimulate transcription of p53-responsive reporter gene.
Zakharova
N I
NI
Sokolov
V V
VV
Rud'ko
V V
VV
Mel'nikov
S V
SV
Vartapetian
A B
AB
Evstaf'eva
A G
AG
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D009154:Mutation; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D013947:Thymosin / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D019913:Nuclear Localization Signals; D011498:Protein Precursors; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C040782:prothymosin alpha; D013947:Thymosin