A mechanism of ubiquitin-independent proteasomal degradation of the tumor suppressors p53 and p73
Protein degradation is an essential and highly regulated process. The proteasomal degradation of the tumor suppressors p53 and p73 is regulated by both polyubiquitination and by an ubiquitin-independent process. Here, we show that this ubiquitin-independent process is mediated by the 20S proteasomes...
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| Veröffentlicht in: | Genes & development 2005-02, Vol.19 (3), p.316-321 |
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| creator | Asher, Gad Tsvetkov, Peter Kahana, Chaim Shaul, Yosef |
| description | Protein degradation is an essential and highly regulated process. The proteasomal degradation of the tumor suppressors p53 and p73 is regulated by both polyubiquitination and by an ubiquitin-independent process. Here, we show that this ubiquitin-independent process is mediated by the 20S proteasomes and is regulated by NQO1. NQO1 physically interacts with p53 and p73 in an NADH-dependent manner and protects them from 20S proteasomal degradation. Remarkably, the vast majority of NQO1 in cells is found in physical association with the 20S proteasomes, suggesting that NQO1 functions as a gatekeeper of the 20S proteasomes. We further show that this pathway plays a role in p53 accumulation in response to ionizing radiation. Our findings provide the first evidence for in vivo degradation of p53 and p73 by the 20S proteasomes and its regulation by NQO1 and NADH level. |
| doi_str_mv | 10.1101/gad.319905 |
| format | Article |
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The proteasomal degradation of the tumor suppressors p53 and p73 is regulated by both polyubiquitination and by an ubiquitin-independent process. Here, we show that this ubiquitin-independent process is mediated by the 20S proteasomes and is regulated by NQO1. NQO1 physically interacts with p53 and p73 in an NADH-dependent manner and protects them from 20S proteasomal degradation. Remarkably, the vast majority of NQO1 in cells is found in physical association with the 20S proteasomes, suggesting that NQO1 functions as a gatekeeper of the 20S proteasomes. We further show that this pathway plays a role in p53 accumulation in response to ionizing radiation. 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The proteasomal degradation of the tumor suppressors p53 and p73 is regulated by both polyubiquitination and by an ubiquitin-independent process. Here, we show that this ubiquitin-independent process is mediated by the 20S proteasomes and is regulated by NQO1. NQO1 physically interacts with p53 and p73 in an NADH-dependent manner and protects them from 20S proteasomal degradation. Remarkably, the vast majority of NQO1 in cells is found in physical association with the 20S proteasomes, suggesting that NQO1 functions as a gatekeeper of the 20S proteasomes. We further show that this pathway plays a role in p53 accumulation in response to ionizing radiation. Our findings provide the first evidence for in vivo degradation of p53 and p73 by the 20S proteasomes and its regulation by NQO1 and NADH level.</description><subject>Animals</subject><subject>Coenzymes - metabolism</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Genes, Tumor Suppressor</subject><subject>Humans</subject><subject>NAD(P)H Dehydrogenase (Quinone) - metabolism</subject><subject>Nuclear Proteins - metabolism</subject><subject>Proteasome Endopeptidase Complex - metabolism</subject><subject>Protein Binding</subject><subject>Protein Interaction Mapping</subject><subject>Research Communications</subject><subject>Tumor Protein p73</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Tumor Suppressor Proteins</subject><subject>Ubiquitin - metabolism</subject><issn>0890-9369</issn><issn>1549-5477</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU1LxDAQhoMoun5c_AGSkweh66RpmubgQcQvELzoOaTpZDfSNjVpBf-9lV38uMwc5nlnBh5CThksGQN2uTLNkjOlQOyQBROFykQh5S5ZQKUgU7xUB-QwpTcAKKEs98kBE2UlcyEWxFzTDu3a9D51NDg61f598qPvM983OOBc-pEOMYxoUuhMSxtcRdOY0Yf-OzCukY5TFyJN0zBETCnERAfBqekbOkh-TPacaROebPsReb27fbl5yJ6e7x9vrp8yWxRszPIaa7QGc2yUQqGcspVF4cDVKIVVBa9KobiprJWVq0BhLUEIbnjlHOSSH5Grzd5hqjts7Px3NK0eou9M_NTBeP1_0vu1XoUPLYpSgJrz59t8DO8TplF3PllsW9NjmJIuZQGQC5jBiw1oY0gpovu5wUB_C9GzEL0RMsNnf7_6RbcG-BdMYImR</recordid><startdate>20050201</startdate><enddate>20050201</enddate><creator>Asher, Gad</creator><creator>Tsvetkov, Peter</creator><creator>Kahana, Chaim</creator><creator>Shaul, Yosef</creator><general>Cold Spring Harbor Laboratory Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20050201</creationdate><title>A mechanism of ubiquitin-independent proteasomal degradation of the tumor suppressors p53 and p73</title><author>Asher, Gad ; Tsvetkov, Peter ; Kahana, Chaim ; Shaul, Yosef</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c441t-2bebecae2ed99e59f9c8ce5f0fbe75c94386593a8cc78f809eb70553a38ff0273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Coenzymes - metabolism</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Genes, Tumor Suppressor</topic><topic>Humans</topic><topic>NAD(P)H Dehydrogenase (Quinone) - metabolism</topic><topic>Nuclear Proteins - metabolism</topic><topic>Proteasome Endopeptidase Complex - metabolism</topic><topic>Protein Binding</topic><topic>Protein Interaction Mapping</topic><topic>Research Communications</topic><topic>Tumor Protein p73</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Tumor Suppressor Proteins</topic><topic>Ubiquitin - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Asher, Gad</creatorcontrib><creatorcontrib>Tsvetkov, Peter</creatorcontrib><creatorcontrib>Kahana, Chaim</creatorcontrib><creatorcontrib>Shaul, Yosef</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genes & development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Asher, Gad</au><au>Tsvetkov, Peter</au><au>Kahana, Chaim</au><au>Shaul, Yosef</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A mechanism of ubiquitin-independent proteasomal degradation of the tumor suppressors p53 and p73</atitle><jtitle>Genes & development</jtitle><addtitle>Genes Dev</addtitle><date>2005-02-01</date><risdate>2005</risdate><volume>19</volume><issue>3</issue><spage>316</spage><epage>321</epage><pages>316-321</pages><issn>0890-9369</issn><eissn>1549-5477</eissn><abstract>Protein degradation is an essential and highly regulated process. The proteasomal degradation of the tumor suppressors p53 and p73 is regulated by both polyubiquitination and by an ubiquitin-independent process. Here, we show that this ubiquitin-independent process is mediated by the 20S proteasomes and is regulated by NQO1. NQO1 physically interacts with p53 and p73 in an NADH-dependent manner and protects them from 20S proteasomal degradation. Remarkably, the vast majority of NQO1 in cells is found in physical association with the 20S proteasomes, suggesting that NQO1 functions as a gatekeeper of the 20S proteasomes. We further show that this pathway plays a role in p53 accumulation in response to ionizing radiation. Our findings provide the first evidence for in vivo degradation of p53 and p73 by the 20S proteasomes and its regulation by NQO1 and NADH level.</abstract><cop>United States</cop><pub>Cold Spring Harbor Laboratory Press</pub><pmid>15687255</pmid><doi>10.1101/gad.319905</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Coenzymes - metabolism DNA-Binding Proteins - metabolism Genes, Tumor Suppressor Humans NAD(P)H Dehydrogenase (Quinone) - metabolism Nuclear Proteins - metabolism Proteasome Endopeptidase Complex - metabolism Protein Binding Protein Interaction Mapping Research Communications Tumor Protein p73 Tumor Suppressor Protein p53 - metabolism Tumor Suppressor Proteins Ubiquitin - metabolism |
| title | A mechanism of ubiquitin-independent proteasomal degradation of the tumor suppressors p53 and p73 |
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