Bookmarking function of p63, a nuclear marker of oral carcinomas

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09927
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57020:Oral pathobiological science-related
• Research Institution: Kanagawa Dental College
• Principal Investigator: Katoh Iyoko 神奈川歯科大学, 歯学部, 特任教授 (20333297)
• Co-Investigator(Kenkyū-buntansha): 倉田 俊一 神奈川歯科大学, 歯学部, 特任教授 (60140901)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: p63 / TP63 / p300 / histone acetylation

Outline of Final Research Achievements

TP63 (p63) is expressed in lower grade head-and-neck carcinomas to block malignant progression by maintaining the epidermal/craniofacial differentiation potential through its epigenetic regulatory functions. To gain insights into histone acetylation at the p63-binding enhancers (book-marking function of p63), we focused on the p63-p300 (histone acetyltransferase) binding process. p63 and p300 segments, as well as their truncated forms, were expressed with different epitope-tags and the nuclear localization signal to analyze the interactions by immunoprecipitation. Results suggest the possibility that a region proximal to the active center of p300 and the extremely C-terminal domain of p63 are involved in the interaction. Unlike many other transcription regulatory factors, p63 could possibly control the acetyltransferase activity.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

近年の研究で、組織分化や癌の悪性転化で起こる遺伝子発現パターンの大きな変化はスーパーエンハンサー形成によるクロマチン・リモデリング、ヒストン・アセチル化等のエピゲノム制御によることが明らかになりつつある。本研究成果は頭頸部癌のエピゲノム制御の中心であるp63とp300の相互作用を解析し、これまで知られていた多数の一般的な転写制御因子とは異なる結合様式を検出した。