Regulation of p53 by the mitotic surveillance/stopwatch pathway: implications in neurodevelopment and cancer.

IF 4.6 2区 生物学 Q2 CELL BIOLOGY Frontiers in Cell and Developmental Biology Pub Date : 2024-09-27 eCollection Date: 2024-01-01 DOI:10.3389/fcell.2024.1451274
Travis H Stracker
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Abstract

The transcription factor p53 (encoded by TP53) plays diverse roles in human development and disease. While best known for its role in tumor suppression, p53 signaling also influences mammalian development by triggering cell fate decisions in response to a wide variety of stresses. After over 4 decades of study, a new pathway that triggers p53 activation in response to mitotic delays was recently identified. Termed the mitotic surveillance or mitotic stopwatch pathway, the USP28 and 53BP1 proteins activate p53 in response to delayed mitotic progression to control cell fate and promote genomic stability. In this Minireview, I discuss its identification, potential roles in neurodevelopmental disorders and cancer, as well as explore outstanding questions about its function, regulation and potential use as a biomarker for anti-mitotic therapies.

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有丝分裂监控/停表途径对 p53 的调控:对神经发育和癌症的影响。
转录因子 p53(由 TP53 编码)在人类发育和疾病中发挥着多种作用。虽然 p53 信号在抑制肿瘤方面的作用最为人熟知,但它还能在各种压力下触发细胞命运决定,从而影响哺乳动物的发育。经过 40 多年的研究,最近发现了一种新的途径,它能触发 p53 激活以应对有丝分裂延迟。USP28 和 53BP1 蛋白被称为有丝分裂监控或有丝分裂秒表途径,它们会激活 p53 以应对有丝分裂进程的延迟,从而控制细胞命运并促进基因组稳定性。在本微型访谈中,我将讨论它的鉴定、在神经发育障碍和癌症中的潜在作用,并探讨有关它的功能、调控和作为抗有丝分裂疗法生物标记物的潜在用途等悬而未决的问题。
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来源期刊
Frontiers in Cell and Developmental Biology
Frontiers in Cell and Developmental Biology Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
9.70
自引率
3.60%
发文量
2531
审稿时长
12 weeks
期刊介绍: Frontiers in Cell and Developmental Biology is a broad-scope, interdisciplinary open-access journal, focusing on the fundamental processes of life, led by Prof Amanda Fisher and supported by a geographically diverse, high-quality editorial board. The journal welcomes submissions on a wide spectrum of cell and developmental biology, covering intracellular and extracellular dynamics, with sections focusing on signaling, adhesion, migration, cell death and survival and membrane trafficking. Additionally, the journal offers sections dedicated to the cutting edge of fundamental and translational research in molecular medicine and stem cell biology. With a collaborative, rigorous and transparent peer-review, the journal produces the highest scientific quality in both fundamental and applied research, and advanced article level metrics measure the real-time impact and influence of each publication.
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