Biomedical subjects

Sun Gwan Hwang

Publications and source records attributed to Sun Gwan Hwang.

4 recordsLinked to original sources

PubMed2003

BRCA1 associates with human papillomavirus type 18 E2 and stimulates E2-dependent transcription.

BRCA1 is a breast and ovarian cancer-related tumor suppressor and has a role in transcriptional activation. We show here that BRCA1 enhances human papillomavirus type 18 (HPV-18) E2-dependent transcription in vivo. Using biochemical approaches, we discovered that BRCA1 interacts with the carboxyl-terminus of HPV-18 E2 protein in vivo and in vitro. Point mutations in the C-terminus make BRCA1 defective in transcriptional activation in E2-dependent transcription. This finding suggests that the C-terminus of BRCA1 is important for E2-dependent transcription. A chromatin immunoprecipitation assay indicated that BRCA1 is recruited onto the E2-dependent promoter region though E2 tethered to E2 binding sites in vivo. These results implicate that BRCA1 plays a role in E2-dependent transcription.

BRCA1 Protein↗

PubMed2002

SWI/SNF complex interacts with tumor suppressor p53 and is necessary for the activation of p53-mediated transcription.

The SWI/SNF complex is required for the transcription of several genes and has been shown to alter nucleosome structure in an ATP-dependent manner. The tumor suppressor protein p53 displays growth and transformation suppression functions that are frequently lost in mutant p53 proteins detected in various cancers. Using genetic and biochemical approaches, we show that several subunits of the human SWI/SNF complex bind to the tumor suppressor protein p53 in vivo and in vitro. The transactivation function of p53 is stimulated by overexpression of hSNF5 and BRG-1 and dominant forms of hSNF5 and BRG-1 repress p53-dependent transcription. Chromatin immunoprecipitation assay shows that hSNF5 and BRG-1 are recruited to a p53-dependent promoter in vivo. Overexpression of dominant negative forms of either hSNF5 or BRG-1 inhibited p53-mediated cell growth suppression and apoptosis. Molecular connection between p53 and the SWI/SNF complex implicates that (i) the SWI/SNF complex is necessary for p53-driven transcriptional activation, and (ii) the SWI/SNF complex plays an important role in p53-mediated cell cycle control.

Adenosine Triphosphatases↗

PubMed2001

Functional interaction between p/CAF and human papillomavirus E2 protein.

p300/CREB-binding protein-associated factor (p/CAF), a transcriptional co-activator, interacts with co-activator p300/CBP and acidic transcription factors. p/CAF mediates transcriptional activation by acetylating nucleosomal histones and cellular factors. Previously we reported that CBP binds to human papillomavirus E2 and activates E2-dependent transcription (Lee, D., Lee, B., Kim, J., Kim, D. W., and Choe, J. (2000) J. Biol. Chem. 275, 7045-7051). Here we show that p/CAF binds to the human papillomavirus E2 protein in vivo and in vitro and activates E2-dependent transcription. CBP along with p/CAF synergistically activates E2-dependent transcription. In addition, the histone acetylase activity of p/CAF is required for efficient activation of E2 transcriptional activity. These results suggest that p/CAF is a transcriptional co-activator of the human papillomavirus E2 protein.

Acetyltransferases↗

PubMed2001

Human papillomavirus type 16 E7 binds to E2F1 and activates E2F1-driven transcription in a retinoblastoma protein-independent manner.

The human papillomavirus (HPV) E7 oncoprotein can immortalize primary human cells and induce tumor formation. These properties of E7 depend on its ability to inhibit the activity of retinoblastoma protein (pRB), which in turn affects E2F function. E2F proteins control the expression of genes involved in differentiation, development, cell proliferation, and apoptosis. By using genetic and biochemical approaches, the present study shows that E7 binds to E2F1 in vivo and in vitro and that both proteins co-localize in the nucleus. Importantly, the binding of the high risk group HPV E7 to E2F1 is tighter than the binding of the low risk group HPV E7 to E2F1. Although E7 of the high risk group HPVs activates E2F1-dependent transcription strongly in C33A or 293T cells, E7 of the low risk group HPVs activates transcription only weakly. By using electrophoretic mobility shift assay, we also showed that E7 binds to E2F1-DNA complexes. Furthermore, we show that these activities of E7 are independent of pRB by using E7 and E2F1 mutants that cannot bind to pRB. Taken together, these data suggest that E7 contributes to the deregulation of pRB-dependent E2F1 repression and to the further activation of E2F1 independently of pRB.

Cell Cycle Proteins↗