Multifunctional transcription factor TFII-I is an activator of BRCA1 function

Abstract

Background:The TFII-I is a multifunctional transcriptional factor known to bind specifically to several DNA sequence elements and to mediate growth factor signalling. A microdeletion at the chromosomal location 7q11.23 encoding TFII-I and the related family of transcription factors may result in the onset of Williams–Beuren syndrome, an autosomal dominant genetic disorder characterised by a unique cognitive profile, diabetes, hypertension, anxiety, and craniofacial defects. Hereditary breast and ovarian cancer susceptibility gene product BRCA1 has been shown to serve as a positive regulator of SIRT1 expression by binding to the promoter region of SIRT1, but cross talk between BRCA1 and TFII-I has not been investigated to date.Methods:A physical interaction between TFII-I and BRCA1 was explored. To determine pathophysiological function of TFII-I, its role as a transcriptional cofactor for BRCA1 was investigated.Results:We found a physical interaction between the carboxyl terminus of TFII-I and the carboxyl terminus of BRCA1, also known as the BRCT domain. Endogenous TFII-I and BRCA1 form a complex in nuclei of intact cells and formation of irradiation-induced nuclear foci was observed. We also showed that the expression of TFII-I stimulates the transcriptional activation function of BRCT by a transient expression assay. The expression of TFII-I also enhanced the transcriptional activation of the SIRT1 promoter mediated by full-length BRCA1.Conclusion:These results revealed the intrinsic mechanism that TFII-I may modulate the cellular functions of BRCA1, and provide important implications to understand the development of breast cancer.

Biochemistry and biology of the inducible multifunctional transcription factor TFII-I: 10years later

“…A recent report indeed connects the two proteins by showing that TFII-I directly interacts with BRCA1 via the BRCT domain of the latter (Tanikawa et al, 2011). This study shows that BRCA1 acts as a transcriptional co-factor for TFII-I and activates the expression of several target genes including SIRT1 and tumor suppressor p53 that are involved in DNA damage checkpoint pathways.…”

p21-activated Kinase-1 Signaling Regulates Transcription of Tissue Factor and Tissue Factor Pathway Inhibitor

“…We found that TF promoter harbors binding sites for some transcription factors already involved in cell growth, proliferation, and cancer-related signaling events. These included TCF-4E, GATA-1, TFII-I, PXR-1:RXR-␣, c-ETS-1, or AP-1/c-Jun (37)(38)(39)(40)(41)(42). Similarly, the involvement of both PAK1 and TF in such processes has been well established (13,33).…”

Cyclin D1 harboring the T286I mutation promotes oncogenic activation in endometrial cancer

“…Immunocytochemistry was performed as previously described (21). The primary antibodies used were the same as those for western blotting.…”