000000859 001__ 859
000000859 005__ 20260306135259.0
000000859 0247_ $$2DOI$$a10.6083/M4MG7MH2
000000859 037__ $$aETD
000000859 245__ $$aPACS-2 regulates SIRT 1-mediated deacetylation of p53 following DNA damage
000000859 269__ $$a2012
000000859 336__ $$aDissertation
000000859 502__ $$bPh.D.
000000859 520__ $$aFollowing DNA damage, p53 activates transcriptional programs that drive cell‑cycle arrest, apoptosis, and senescence, and these outcomes depend on regulation by cofactors and post‑translational modifications. Because SIRT1 deacetylates and represses p53, mechanisms controlling the SIRT1–p53 axis are critical for effective DNA damage responses. This study identifies the membrane‑trafficking protein PACS‑2 as an inhibitor of SIRT1‑mediated p53 deacetylation. PACS‑2 directly binds SIRT1, promotes p53 acetylation, and supports p21 expression. Loss of PACS‑2 decreases p53 acetylation and increases apoptosis in a SIRT1‑, p53‑, and p21‑dependent manner. These findings establish PACS‑2 as a key regulator of the SIRT1–p53–p21 pathway during DNA damage.
000000859 540__ $$fCC BY
000000859 542__ $$fIn copyright - single owner
000000859 650__ $$aSirtuins$$034850
000000859 650__ $$aMembrane Proteins$$022009
000000859 650__ $$aDNA Damage$$017979
000000859 650__ $$aViral Proteins$$027836
000000859 650__ $$aVesicular Transport Proteins$$034519
000000859 650__ $$aCarrier Proteins$$016184
000000859 650__ $$aViral Regulatory and Accessory Proteins$$037771
000000859 650__ $$aApoptosis Regulatory Proteins$$036672
000000859 650__ $$aSirtuin 1$$038627
000000859 6531_ $$ap53-aip1 (p53-regulated apoptosis inducing protein 1)
000000859 6531_ $$apacs-2 phosphofurin acidic cluster sorting protein-2)
000000859 691__ $$aSchool of Medicine$$041369
000000859 692__ $$aDepartment of Cell, Developmental and Cancer Biology$$041399
000000859 7001_ $$aAtkins, Katelyn$$uOregon Health and Science University$$041354
000000859 7201_ $$aThomas, Gary$$uOregon Health and Science University$$041354$$7Personal$$eMentor
000000859 8564_ $$9e22f4c4a-de43-4fe3-b4a3-f3b4eceb7383$$s11334325$$uhttps://digitalcollections.ohsu.edu/record/859/files/862_etd.pdf$$ePublic$$2f753d2e0de7ef5ca9c43cd31b972d161$$31
000000859 905__ $$a/rest/prod/3r/07/4t/95/3r074t95s
000000859 909CO $$ooai:digitalcollections.ohsu.edu:859$$pstudent-work
000000859 956__ $$aGet Accessible Copy$$uhttps://ohsu.libwizard.com/f/requestaccessibledocument
000000859 980__ $$aTheses and Dissertations