Regulation of prothymosin alpha during the cell cycle.
A number of studies have indicated that the small nuclear acidic protein prothymosin alpha is associated with cellular-proliferation events. For example, c-myc causes immediate transcriptional activation of prothymosin alpha, and prothymosin alpha antisense oligonucleotides inhibit myeloma cell division. To investigate the regulation of prothymosin alpha, we examined its mRNA and protein levels during the cell cycle of mononuclear cells and fibroblastic cells. We isolated immunoreactive material from cellular extracts and immunolocalized the protein to the nucleus during the cell cycle. We reported here that the material present in the cells is prothymosin alpha rather than the amino-terminal peptide thymosin alpha 1. [3H]Thymidine-incorporation studies associate maximum accumulation of mRNA and protein with the S/G2 phase of the cell cycle. This induction of prothymosin alpha mRNA seems to resemble cyclin B expression and is more pronounced in fibroblasts. Moreover, transient-transfection experiments indicate that transcription factor E2F is a strong positive regulator of the prothymosin alpha gene. Our results are consistent with the hypothesis that prothymosin alpha is involved in proliferation checkpoints of the cell cycle.
Vareli
K
K
Laboratory of Biological Chemistry, University of Ioannina Medical School, Ioannina, Greece.
Tsolas
O
O
Frangou-Lazaridis
M
M
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D003470:Culture Media; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D016195:G2 Phase; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D056465:Retinoblastoma-Binding Protein 1; D016196:S Phase; D013947:Thymosin / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003470:Culture Media; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D011498:Protein Precursors; D012333:RNA, Messenger; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; C040782:prothymosin alpha; D013947:Thymosin