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Role of Pirh2 in mediating the regulation of p53 and c-Myc
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نویسنده
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hakem a. ,bohgaki m. ,lemmers b. ,tai e. ,salmena l. ,matysiak-zablocki e. ,jung y.-s. ,karaskova j. ,kaustov l. ,duan s. ,madore j. ,boutros p. ,sheng y. ,chesi m. ,bergsagel p.l. ,perez-ordonez b. ,mes-masson a.-m. ,penn l. ,squire j. ,chen x. ,jurisica i. ,arrowsmith c. ,sanchez o. ,benchimol s. ,hakem r.
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منبع
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plos genetics - 2011 - دوره : 7 - شماره : 11
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چکیده
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Ubiquitylation is fundamental for the regulation of the stability and function of p53 and c-myc. the e3 ligase pirh2 has been reported to polyubiquitylate p53 and to mediate its proteasomal degradation. here,using pirh2 deficient mice,we report that pirh2 is important for the in vivo regulation of p53 stability in response to dna damage. we also demonstrate that c-myc is a novel interacting protein for pirh2 and that pirh2 mediates its polyubiquitylation and proteolysis. pirh2 mutant mice display elevated levels of c-myc and are predisposed for plasma cell hyperplasia and tumorigenesis. consistent with the role p53 plays in suppressing c-myc-induced oncogenesis,its deficiency exacerbates tumorigenesis of pirh2-/- mice. we also report that low expression of human pirh2 in lung,ovarian,and breast cancers correlates with decreased patients' survival. collectively,our data reveal the in vivo roles of pirh2 in the regulation of p53 and c-myc stability and support its role as a tumor suppressor. © 2011 hakem et al.
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آدرس
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ontario cancer institute,university health network,department of medical biophysics,university of toronto,toronto, Canada, ontario cancer institute,university health network,department of medical biophysics,university of toronto,toronto, Canada, institut de génétique moléculaire de montpellier,cnrs-umr 5535,montpellier, France, department of biology,york university,toronto, Canada, cancer genetics program,beth israel deaconess cancer center,department of medicine,harvard medical school,boston,ma, United States, ontario cancer institute,university health network,department of medical biophysics,university of toronto,toronto, Canada, university of california davis,davis,ca, United States, ontario cancer institute,university health network,department of medical biophysics,university of toronto,toronto, Canada, ontario cancer institute,university health network,department of medical biophysics,university of toronto,toronto, Canada, ontario cancer institute,university health network,department of medical biophysics,university of toronto,toronto, Canada, institut du cancer de montréal,montréal, Canada, ontario cancer institute,university health network,department of medical biophysics,university of toronto,toronto, Canada, ontario cancer institute,university health network,department of medical biophysics,university of toronto,toronto, Canada, comprehensive cancer center,mayo clinic arizona,scottsdale,az, United States, comprehensive cancer center,mayo clinic arizona,scottsdale,az, United States, university health network and department of pathology,university of toronto,toronto, Canada, institut du cancer de montréal,montréal, Canada, ontario cancer institute,university health network,department of medical biophysics,university of toronto,toronto, Canada, queen's university,kingston, Canada, university of california davis,davis,ca, United States, ontario cancer institute,university health network,department of medical biophysics,university of toronto,toronto, Canada, ontario cancer institute,university health network,department of medical biophysics,university of toronto,toronto, Canada, university of ontario institute of technology,oshawa, Canada, department of biology,york university,toronto, Canada, ontario cancer institute,university health network,department of medical biophysics,university of toronto,toronto, Canada
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Authors
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