A Novel Interaction between TFII-I and Mdm2 with a Negative Effect on TFII-I Transcriptional Activity
| Autoři | |
|---|---|
| Rok publikování | 2015 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Plos one |
| Fakulta / Pracoviště MU | |
| Citace | |
| Doi | http://dx.doi.org/10.1371/journal.pone.0144753 |
| Obor | Genetika a molekulární biologie |
| Klíčová slova | IMMUNODEFICIENCY-VIRUS TYPE-1; WILLIAMS-BEUREN-SYNDROME; P53 TUMOR-SUPPRESSOR; LONG TERMINAL REPEAT; HISTONE DEACETYLASE-3; HUMAN CYTOMEGALOVIRUS; P53-INDEPENDENT ROLE; HIV-1 TRANSCRIPTION; ACIDIC DOMAIN; CELL-CYCLE |
| Popis | Williams-Beuren syndrome-associated transcription factor TFII-I plays a critical regulatory role in bone and neural tissue development and in immunity, in part by regulating cell proliferation in response to mitogens. Mdm2, a cellular oncogene responsible for the loss of p53 tumor suppressor activity in a significant proportion of human cancers, was identified in this study as a new binding partner for TFII-I and a negative regulator of TFII-I-mediated transcription. These findings suggest a new p53-independent mechanism by which increased Mdm2 levels found in human tumors could influence cancer cells. In addition to that, we present data indicating that TFII-I is an important cellular regulator of transcription from the immediate-early promoter of human cytomegalovirus, a promoter sequence frequently used in mammalian expression vectors, including vectors for gene therapy. Our observation that Mdm2 over-expression can decrease the ability of TFII-I to activate the CMV promoter might have implications for the efficiency of experimental gene therapy based on CMV promoter-derived vectors in cancers with Mdm2 gene amplification. |
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