NDLI: A USP28-53BP1-p53-p21 signaling axis arrests growth after centrosome loss or prolonged mitosis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lambrus, Bramwell G. Uetake, Yumi Scott, Phillip M. Clutario, Kevin M. Daggubati, Vikas Sluder, Greenfield Holland, Andrew J.
Description	Author Affiliation: Lambrus BG ( Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.); Daggubati V ( Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.); Uetake Y ( Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655.); Scott PM ( Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.); Clutario KM ( Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.); Sluder G ( Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655.); Holland AJ ( Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205 aholland@jhmi.edu.)
Abstract	Precise regulation of centrosome number is critical for accurate chromosome segregation and the maintenance of genomic integrity. In nontransformed cells, centrosome loss triggers a p53-dependent surveillance pathway that protects against genome instability by blocking cell growth. However, the mechanism by which p53 is activated in response to centrosome loss remains unknown. Here, we have used genome-wide CRISPR/Cas9 knockout screens to identify a USP28-53BP1-p53-p21 signaling axis at the core of the centrosome surveillance pathway. We show that USP28 and 53BP1 act to stabilize p53 after centrosome loss and demonstrate this function to be independent of their previously characterized role in the DNA damage response. Surprisingly, the USP28-53BP1-p53-p21 signaling pathway is also required to arrest cell growth after a prolonged prometaphase. We therefore propose that centrosome loss or a prolonged mitosis activate a common signaling pathway that acts to prevent the growth of cells that have an increased propensity for mitotic errors.
ISSN	00219525
e-ISSN	15408140
Journal	The Journal of Cell Biology
Issue Number	2
Volume Number	214
Language	English
Publisher	Rockefeller University Press (United States)
Publisher Date	2016-07-18
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cell Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine

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