First Author | Darbinian N | Year | 1999 |
Journal | Oncogene | Volume | 18 |
Issue | 46 | Pages | 6398-402 |
PubMed ID | 10597240 | Mgi Jnum | J:113789 |
Mgi Id | MGI:3687670 | Doi | 10.1038/sj.onc.1203011 |
Citation | Darbinian N, et al. (1999) Association of Pur alpha and E2F-1 suppresses transcriptional activity of E2F-1. Oncogene 18(46):6398-402 |
abstractText | Protein-protein interaction can play an important role in the control of several biological events including gene transcription, replication and cell proliferation. E2F-1 is a DNA-binding transcription factor which, upon interaction with its target DNA sequence, induces expression of several S phase specific genes allowing progression of the cell cycle. Evidently, the activity of this protein is modulated by its cellular partner, pRb, which in the hypophosphorylated form, binds to E2F-1 and inactivates its transcriptional ability. In this study, we have demonstrated that expression of a sequence-specific single-stranded DNA binding protein, Pur alpha, in cells decreases the ability of E2F-1 to exert its transcriptional activity upon the responsive promoter derived from DHFR. Results from band shift experiments revealed that while Pur alpha does not recognize the double-stranded DNA fragment containing the E2F-1 binding site, it has the ability to inhibit E2F-1 interaction with its target DNA sequence. Results from GST pull-down assays and the combined immunoprecipitation/Western blot analysis of nuclear extracts revealed a direct association of E2F-1 with Pur alpha in the absence of the DNA molecule containing the E2F-1 binding site. The association of Pur alpha with E2F-1 may increase the stability of E2F-1, as a higher level of E2F-1 was detected in cells coexpressing Pur alpha and E2F-1. The importance of these observations with respect to the role of Pur alpha in the control of cell cycle progression is discussed. |