Nuclear stabilization of p53 requires a functional nucleolar surveillance pathway

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Fältnamn	Indikatorer	Metadata
000		05032naa a2200757 4500
001		oai:lup.lub.lu.se:bfdf686f-3b20-4dfa-a4d8-9db4536f7f0f
003		SwePub
008		221213s2022 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://lup.lub.lu.se/record/bfdf686f-3b20-4dfa-a4d8-9db4536f7f0f2 URI
024	7	a https://doi.org/10.1016/j.celrep.2022.1115712 DOI
040		a (SwePub)lu
041		a engb eng
042		9 SwePub
072	7	a art2 swepub-publicationtype
072	7	a ref2 swepub-contenttype
100	1	a Hannan, Katherine M.u Peter MacCallum Cancer Centre,University of Melbourne4 aut
245	1 0	a Nuclear stabilization of p53 requires a functional nucleolar surveillance pathway
264	1	b Elsevier BV,c 2022
520		a The nucleolar surveillance pathway monitors nucleolar integrity and responds to nucleolar stress by mediating binding of ribosomal proteins to MDM2, resulting in p53 accumulation. Inappropriate pathway activation is implicated in the pathogenesis of ribosomopathies, while drugs selectively activating the pathway are in trials for cancer. Despite this, the molecular mechanism(s) regulating this process are poorly understood. Using genome-wide loss-of-function screens, we demonstrate the ribosome biogenesis axis as the most potent class of genes whose disruption stabilizes p53. Mechanistically, we identify genes critical for regulation of this pathway, including HEATR3. By selectively disabling the nucleolar surveillance pathway, we demonstrate that it is essential for the ability of all nuclear-acting stresses, including DNA damage, to induce p53 accumulation. Our data support a paradigm whereby the nucleolar surveillance pathway is the central integrator of stresses that regulate nuclear p53 abundance, ensuring that ribosome biogenesis is hardwired to cellular proliferative capacity.
650	7	a NATURVETENSKAPx Biologix Biokemi och molekylärbiologi0 (SwePub)106022 hsv//swe
650	7	a NATURAL SCIENCESx Biological Sciencesx Biochemistry and Molecular Biology0 (SwePub)106022 hsv//eng
653		a CP: Molecular biology
653		a high-content screening
653		a high-throughput screening
653		a nucleolar surveillance pathway
653		a nucleolus
653		a p53
653		a ribosomal proteins
653		a ribosome biogenesis
653		a stress
700	1	a Soo, Priscillau Australian National University4 aut
700	1	a Wong, Mei S.u Peter MacCallum Cancer Centre,University of Melbourne4 aut
700	1	a Lee, Justine K.u University of Newcastle upon Tyne4 aut
700	1	a Hein, Nadineu Australian National University4 aut
700	1	a Poh, Perlitau Australian National University4 aut
700	1	a Wysoke, Kira D.u Australian National University4 aut
700	1	a Williams, Tobias D.4 aut
700	1	a Montellese, Christianu ETH Zürich4 aut
700	1	a Smith, Lorey K.u Peter MacCallum Cancer Centre4 aut
700	1	a Al-Obaidi, Sheren J.4 aut
700	1	a Núñez-Villacís, Lorena4 aut
700	1	a Pavy, Megan4 aut
700	1	a He, Jin Shuu Australian National University4 aut
700	1	a Parsons, Kate M.u Australian National University4 aut
700	1	a Loring, Karagh E.4 aut
700	1	a Morrison, Tess4 aut
700	1	a Diesch, Jeannineu Peter MacCallum Cancer Centre4 aut
700	1	a Burgio, Gaetan4 aut
700	1	a Ferreira, Rita4 aut
700	1	a Feng, Zhi Ping4 aut
700	1	a Gould, Cathryn M.u Peter MacCallum Cancer Centre4 aut
700	1	a Madhamshettiwar, Piyush B.u Peter MacCallum Cancer Centre4 aut
700	1	a Flygare, Johanu Lund University,Lunds universitet,Stamceller till röda blodkroppar,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Stem Cells to Red Blood Cells,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments4 aut0 (Swepub:lu)molm-jfl
700	1	a Gonda, Thomas J.u University of Queensland4 aut
700	1	a Simpson, Kaylene J.u University of Melbourne,Peter MacCallum Cancer Centre4 aut
700	1	a Kutay, Ulrikeu ETH Zürich4 aut
700	1	a Pearson, Richard B.u University of Melbourne,Monash University,Peter MacCallum Cancer Centre4 aut
700	1	a Engel, Christophu University of Regensburg4 aut
700	1	a Watkins, Nicholas J.u University of Newcastle upon Tyne4 aut
700	1	a Hannan, Ross D.u Monash University,ETH Zürich,University of Melbourne,University of Queensland,Peter MacCallum Cancer Centre4 aut
700	1	a George, Amee J.u University of Melbourne,Australian National University4 aut
710	2	a Peter MacCallum Cancer Centreb University of Melbourne4 org
773	0	t Cell Reportsd : Elsevier BVg 41:5q 41:5x 2211-1247
856	4	u http://dx.doi.org/10.1016/j.celrep.2022.111571x freey FULLTEXT
856	4 8	u https://lup.lub.lu.se/record/bfdf686f-3b20-4dfa-a4d8-9db4536f7f0f
856	4 8	u https://doi.org/10.1016/j.celrep.2022.111571

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