Functional Activation of ATM by the Prostate Cancer Suppressor NKX3.1

dc.contributor.utaustinauthorLee, Jeong-Hoen_US
dc.contributor.utaustinauthorPaull, Tanya T.en_US
dc.creatorCai, Bowen W.en_US
dc.creatorJu, J. H.en_US
dc.creatorLee, Jeong-Hoen_US
dc.creatorPaull, Tanya T.en_US
dc.creatorGelmann, Edward P.en_US
dc.date.accessioned2016-10-28T19:51:19Z
dc.date.available2016-10-28T19:51:19Z
dc.date.issued2013-08en_US
dc.description.abstractThe prostate tumor suppressor NKX3.1 augments response to DNA damage and enhances survival after DNA damage. Within minutes of DNA damage, NKX3.1 undergoes phosphorylation at tyrosine 222, which is required for a functional interaction with ataxia telangiectasia mutated (ATM) kinase. NKX3.1 binds to the N-terminal region of ATM, accelerates ATM activation, and hastens the formation of gamma histone2AX. NKX3.1 enhances DNA-dependent ATM kinase activation by both the MRN complex and H2O2 in a DNA-damage-independent manner. ATM, bound to the NKX3.1 homeodomain, phosphorylates NKX3.1, leading to ubiquitination and degradation. Thus, NKX3.1 and ATM have a functional interaction leading to ATM activation and then NKX3.1 degradation in a tightly regulated DNA damage response specific to prostate epithelial cells. These findings demonstrate a mechanism for the tumor-suppressor properties of NKX3.1, demonstrate how NKX3.1 may enhance DNA integrity in prostate stem cells and may help to explain how cells differ in their sensitivity to DNA damage.en_US
dc.description.departmentCellular and Molecular Biologyen_US
dc.description.sponsorshipCA132813, NCI NIH HHSen_US
dc.description.sponsorshipCA154293, NCI NIH HHSen_US
dc.description.sponsorshipP01 CA154293, NCI NIH HHSen_US
dc.description.sponsorshipP30 CA013696-36, NCI NIH HHSen_US
dc.identifierdoi:10.15781/T24Q7QS82
dc.identifier.citationBowen, Cai, Jeong-Ho Ju, Ji-Hoon Lee, Tanya T. Paull, and Edward P. Gelmann. "Functional activation of ATM by the prostate cancer suppressor NKX3. 1." Cell reports, Vol. 4, No. 3 (Aug., 2013): 516-529.en_US
dc.identifier.doi10.1016/j.celrep.2013.06.039en_US
dc.identifier.issn2211-1247en_US
dc.identifier.urihttp://hdl.handle.net/2152/43237
dc.language.isoEnglishen_US
dc.relation.ispartofen_US
dc.relation.ispartofserialCell Reportsen_US
dc.rightsAdministrative deposit of works to Texas ScholarWorks: This works author(s) is or was a University faculty member, student or staff member; this article is already available through open access or the publisher allows a PDF version of the article to be freely posted online. The library makes the deposit as a matter of fair use (for scholarly, educational, and research purposes), and to preserve the work and further secure public access to the works of the University.en_US
dc.rights.restrictionOpenen_US
dc.subjectbase excision-repairen_US
dc.subjectdouble-strand breaksen_US
dc.subjectdna-damage responseen_US
dc.subjectmre11/rad50/nbs1 complexen_US
dc.subjectoxidative stressen_US
dc.subjecttopoisomerase-ien_US
dc.subjectprotein-kinaseen_US
dc.subjectexpressionen_US
dc.subjectgenomeen_US
dc.subjectcellsen_US
dc.subjectcell biologyen_US
dc.titleFunctional Activation of ATM by the Prostate Cancer Suppressor NKX3.1en_US
dc.typeArticleen_US

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