000000516 001__ 516
000000516 005__ 20260422113048.0
000000516 0247_ $$2DOI$$a10.6083/M4639MQ0
000000516 037__ $$aETD
000000516 245__ $$aRegulation of the P53-MDM2 feedback loop by nucleostemin and ribosomal proteins
000000516 260__ $$bOregon Health and Science University
000000516 269__ $$a2007
000000516 336__ $$aDissertation
000000516 502__ $$bPh.D.
000000516 502__ $$gMolecular & Medical Genetics (sunsetting)
000000516 520__ $$aThe MDM2–p53 feedback loop is tightly regulated to restrain inappropriate p53 activation while allowing rapid cellular stress responses. This dissertation investigates regulation of this pathway by the nucleolar protein nucleostemin (NS) and ribosomal proteins L5, L11, and L23. NS was found to bind the acidic domain of MDM2, inhibit its E3 ubiquitin ligase activity, and stabilize p53, leading to p21 induction and cell‑cycle arrest. Both overexpression and depletion of NS activated p53, indicating that aberrant NS levels disrupt cellular homeostasis. Nucleolar stress induced by mycophenolic acid or 5‑fluorouracil promoted release of NS and ribosomal proteins from the nucleolus, enhancing their interaction with MDM2 and activation of p53. These findings identify the nucleolus as a key stress sensor and reveal cooperative roles for NS and ribosomal proteins in modulating the MDM2–p53 pathway.
000000516 540__ $$fCC BY
000000516 542__ $$fIn copyright - single owner
000000516 650__ $$aPhysiology$$024123
000000516 650__ $$aRibosomal Proteins$$025489
000000516 650__ $$aProto-Oncogene Proteins c-mdm2$$036972
000000516 650__ $$aTumor Suppressor Protein p53$$028922
000000516 691__ $$aSchool of Medicine$$041369
000000516 692__ $$aDepartment of Molecular and Medical Genetics$$041428
000000516 7001_ $$aSun, Xiaoxin$$uOregon Health and Science University$$041354
000000516 7201_ $$aLu, Hua$$uOregon Health and Science University$$041354$$7Personal$$eAdvisor
000000516 7201_ $$aHurlin, Peter$$uOregon Health and Science University$$041354$$7Personal$$eChair
000000516 8564_ $$9bcfb0d03-d03c-44c5-a721-d3c5fd33ad6e$$s1289197$$uhttps://digitalcollections.ohsu.edu/record/516/files/517_etd.pdf$$ePublic$$20bd2a00d42f9dc99be6e4e4cbbcd16af$$31
000000516 901__ $$a<p>These documents are archival records. They are retained for historical reference only. </p><p><b>Need an accessible version? Use the ‘Get Accessible Copy’ link above.</b></p>
000000516 905__ $$a/rest/prod/x6/33/f1/04/x633f104m
000000516 909CO $$ooai:digitalcollections.ohsu.edu:516$$pstudent-work
000000516 956__ $$aGet Accessible Copy$$uhttps://ohsu.libwizard.com/f/requestaccessibledocument
000000516 980__ $$aTheses and Dissertations