Mdm2 targets the p53 transcription cofactor JMY for degradation.
We define here a new mechanism through which Mdm2 (mouse double minute 2) regulates p53 activity, by targeting the p53 transcription cofactor JMY. DNA damage causes an increase in JMY protein, and, in a similar manner, small molecule inhibitors of Mdm2 activity induce JMY in unperturbed cells. At a...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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2007
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| _version_ | 1797062355768573952 |
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| author | Coutts, A Boulahbel, H Graham, A La Thangue, N |
| author_facet | Coutts, A Boulahbel, H Graham, A La Thangue, N |
| author_sort | Coutts, A |
| collection | OXFORD |
| description | We define here a new mechanism through which Mdm2 (mouse double minute 2) regulates p53 activity, by targeting the p53 transcription cofactor JMY. DNA damage causes an increase in JMY protein, and, in a similar manner, small molecule inhibitors of Mdm2 activity induce JMY in unperturbed cells. At a mechanistic level, Mdm2 regulation of JMY requires the Mdm2 RING (really interesting new gene) finger, which promotes the ubiquitin-dependent degradation of JMY. However, regulation of JMY occurs independently of the p53-binding domain in Mdm2 and p53 activity. These results define a new functional relationship between the p53 cofactor JMY and Mdm2, and indicate that transcription cofactors that facilitate p53 activity are important targets for Mdm2 in suppressing the p53 response. |
| first_indexed | 2024-03-06T20:44:22Z |
| format | Journal article |
| id | oxford-uuid:355b2ad1-9807-483f-beb4-427936a72544 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:44:22Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:355b2ad1-9807-483f-beb4-427936a725442022-03-26T13:31:33ZMdm2 targets the p53 transcription cofactor JMY for degradation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:355b2ad1-9807-483f-beb4-427936a72544EnglishSymplectic Elements at Oxford2007Coutts, ABoulahbel, HGraham, ALa Thangue, NWe define here a new mechanism through which Mdm2 (mouse double minute 2) regulates p53 activity, by targeting the p53 transcription cofactor JMY. DNA damage causes an increase in JMY protein, and, in a similar manner, small molecule inhibitors of Mdm2 activity induce JMY in unperturbed cells. At a mechanistic level, Mdm2 regulation of JMY requires the Mdm2 RING (really interesting new gene) finger, which promotes the ubiquitin-dependent degradation of JMY. However, regulation of JMY occurs independently of the p53-binding domain in Mdm2 and p53 activity. These results define a new functional relationship between the p53 cofactor JMY and Mdm2, and indicate that transcription cofactors that facilitate p53 activity are important targets for Mdm2 in suppressing the p53 response. |
| spellingShingle | Coutts, A Boulahbel, H Graham, A La Thangue, N Mdm2 targets the p53 transcription cofactor JMY for degradation. |
| title | Mdm2 targets the p53 transcription cofactor JMY for degradation. |
| title_full | Mdm2 targets the p53 transcription cofactor JMY for degradation. |
| title_fullStr | Mdm2 targets the p53 transcription cofactor JMY for degradation. |
| title_full_unstemmed | Mdm2 targets the p53 transcription cofactor JMY for degradation. |
| title_short | Mdm2 targets the p53 transcription cofactor JMY for degradation. |
| title_sort | mdm2 targets the p53 transcription cofactor jmy for degradation |
| work_keys_str_mv | AT couttsa mdm2targetsthep53transcriptioncofactorjmyfordegradation AT boulahbelh mdm2targetsthep53transcriptioncofactorjmyfordegradation AT grahama mdm2targetsthep53transcriptioncofactorjmyfordegradation AT lathanguen mdm2targetsthep53transcriptioncofactorjmyfordegradation |