p63：发育、衰老、老化与癌症之间十字路口的主要调节因子

p63: A Master Regulator at the Crossroads Between Development, Senescence, Aging, and Cancer.

作者信息

Sadu Murari Lakshana Sruthi, Kunkel Sam, Shetty Anala, Bents Addison, Bhandary Aayush, Rivera-Mulia Juan Carlos

机构信息

Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Medical School, Minneapolis, MN 55455, USA.

Stem Cell Institute, University of Minnesota Medical School, Minneapolis, MN 55455, USA.

出版信息

Cells. 2025 Jan 3;14(1):43. doi: 10.3390/cells14010043.

DOI:10.3390/cells14010043

PMID:39791744

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11719615/

Abstract

The p63 protein is a master regulatory transcription factor that plays crucial roles in cell differentiation, adult tissue homeostasis, and chromatin remodeling, and its dysregulation is associated with genetic disorders, physiological and premature aging, and cancer. The effects of p63 are carried out by two main isoforms that regulate cell proliferation and senescence. p63 also controls the epigenome by regulating interactions with histone modulators, such as the histone acetyltransferase p300, deacetylase HDAC1/2, and DNA methyltransferases. miRNA-p63 interactions are also critical regulators in the context of cancer metastasis. This review aims to elaborate on the diverse roles of p63, focusing on disease, development, and the mechanisms controlling genome organization and function.

摘要

p63蛋白是一种主要的调控转录因子，在细胞分化、成体组织稳态和染色质重塑中发挥关键作用，其失调与遗传疾病、生理衰老和早衰以及癌症相关。p63的作用由两种主要的异构体执行，它们调节细胞增殖和衰老。p63还通过调节与组蛋白调节剂（如组蛋白乙酰转移酶p300、脱乙酰酶HDAC1/2和DNA甲基转移酶）的相互作用来控制表观基因组。miRNA-p63相互作用在癌症转移方面也是关键的调节因子。本综述旨在阐述p63的多种作用，重点关注疾病、发育以及控制基因组组织和功能的机制。