Epigenetic Regulator BRD4 in Gene Reprogramming and Cancer Therapy

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  • 2016-06-16


[BK21 Plus Seminar]

▶Subject: Epigenetic Regulator BRD4 in Gene Reprogramming and Cancer Therapy

▶Speaker: Cheng-Ming Chiang, Ph.D. (University of Texas Southwestern Medical Center)

▶Date: 2:00 PM/June. 22(Wed.)/2016

▶Place: Life Science Bldg. #104

Bromodomain-containing protein 4 (BRD4) is an epigenetic reader protein recognizing acetyl-lysine in histones and nonhistone proteins via its N-terminal tandem bromodomains. Although BRD4 is a universal chromatin-binding factor, functional inactivation of BRD4 surprisingly shows select effects on target gene transcription. Emerging data also implicate BRD4 in diverse cellular processes including cell cycle progression, DNA damage response, chromatin structure maintenance, stem cell reprogramming, viral latency and reactivation, and cancer development and therapeutics. These multifunctional effects of BRD4 are regulated in part by casein kinase II (CK2)-mediated phosphorylation and protein phosphatase 2A (PP2A)-mediated dephosphorylation that in turn modulate BRD4 interaction with different cellular and viral proteins. Phosphorylation-regulated BRD4 function dictates G9a lysine methyltransferase activity in methylating histone H3 and p53 tumor suppressor as well as functional recruitment of human papillomavirus (HPV) E2 transcription/replication factor to targeted HPV and cellular gene promoters. The molecular switch controlled by cancer cell-addicted CK2 activity highlights the elegance of phosphorylation-regulated intra- and inter-molecular contact switches in modulating BRD4 function in gene-specific targeting and pathway selectivity. A new class of small compounds targeting this phospho region of BRD4 provides a more selective inhibition of gene transcription compared to the widely used JQ1- and I-BET-derived bromodomain inhibitors.

▶Inquiry: Prof. Cho, Yunje (279-2288)
* This seminar will be given in English.
please refrain from taking photos during seminars. *