The deubiquitination enzyme USP46 functions as a tumor suppressor by controlling PHLPP-dependent attenuation of Akt signaling in colon cancer
PH domain leucine-rich-repeats protein phosphatase (PHLPP) is a family of Ser/Thr protein phosphatases that serve as tumor suppressors by negatively regulating Akt. Our recent studies have demonstrated that the ubiquitin proteasome pathway has an important role in the downregulation of PHLPP in colo...
Gespeichert in:
| Veröffentlicht in: | Oncogene 2013-01, Vol.32 (4), p.471-478 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 478 |
|---|---|
| container_issue | 4 |
| container_start_page | 471 |
| container_title | Oncogene |
| container_volume | 32 |
| creator | Li, X Stevens, P D Yang, H Gulhati, P Wang, W Evers, B M Gao, T |
| description | PH domain leucine-rich-repeats protein phosphatase (PHLPP) is a family of Ser/Thr protein phosphatases that serve as tumor suppressors by negatively regulating Akt. Our recent studies have demonstrated that the ubiquitin proteasome pathway has an important role in the downregulation of PHLPP in colorectal cancer. In this study, we show that the deubiquitinase USP46 stabilizes the expression of both PHLPP isoforms by reducing the rate of PHLPP degradation. USP46 binds to PHLPP and directly removes the polyubiquitin chains from PHLPP
in vitro
and in cells. Increased USP46 expression correlates with decreased ubiquitination and upregulation of PHLPP proteins in colon cancer cells, whereas knockdown of USP46 has the opposite effect. Functionally, USP46-mediated stabilization of PHLPP and the subsequent inhibition of Akt result in a decrease in cell proliferation and tumorigenesis of colon cancer cells
in vivo
. Moreover, reduced USP46 protein level is found associated with poor PHLPP expression in colorectal cancer patient specimens. Taken together, these results indentify a tumor suppressor role of USP46 in promoting PHLPP expression and inhibiting Akt signaling in colon cancer. |
| doi_str_mv | 10.1038/onc.2012.66 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3371166</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A318345070</galeid><sourcerecordid>A318345070</sourcerecordid><originalsourceid>FETCH-LOGICAL-c546t-299ae190881b21b0186b33aa931cefcc8b4ae4387053a56e5cc505c4fe761c4d3</originalsourceid><addsrcrecordid>eNptkt9r1TAUx4so7jp98l0Cvgjaa340afsyuAx1wgUvuD2HND3tMtukSxrh-j_4P5vuzrnJSCDhnM_5Jt_kZNlrgtcEs-qjs3pNMaFrIZ5kK1KUIue8Lp5mK1xznNeU0aPsRQhXGOOyxvR5dkQpqwkXbJX9Pr8E1EJszHU0s7FqNs4isL_2I6CL77tCoC5avUQDUmmiOY7OoxCnyUMIadvskXZ29m4YjO3R7my72-UtTGBbsDNS8ww2HnRdhzY_ZhRMb9UNbGyqHVJGK6vBv8yedWoI8Op2Pc4uPn86Pz3Lt9--fD3dbHPNCzHntK4VkBpXFWkoaTCpRMOYUjUjGjqtq6ZQULCqxJwpLoBrzTHXRQelILpo2XF2ctCdYjNCq9M9vRrk5M2o_F46ZeTDjDWXsnc_JWMlIUIkgXe3At5dRwizHE3QMAzKgotBElpxXBcclwl9-x965aJP_heqpIwxwcQ_qlcDSGM7l87Vi6jcMFKxRQonav0IlUYLo0mfAJ1J8QcF7w8F2rsQPHR3HgmWS_fI1D1y6R554-rN_We5Y_-2SwI-HICQUrYHf8_LI3p_AFEDz-E</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1272333636</pqid></control><display><type>article</type><title>The deubiquitination enzyme USP46 functions as a tumor suppressor by controlling PHLPP-dependent attenuation of Akt signaling in colon cancer</title><source>MEDLINE</source><source>SpringerLink_现刊</source><source>Nature</source><source>EZB Electronic Journals Library</source><creator>Li, X ; Stevens, P D ; Yang, H ; Gulhati, P ; Wang, W ; Evers, B M ; Gao, T</creator><creatorcontrib>Li, X ; Stevens, P D ; Yang, H ; Gulhati, P ; Wang, W ; Evers, B M ; Gao, T</creatorcontrib><description>PH domain leucine-rich-repeats protein phosphatase (PHLPP) is a family of Ser/Thr protein phosphatases that serve as tumor suppressors by negatively regulating Akt. Our recent studies have demonstrated that the ubiquitin proteasome pathway has an important role in the downregulation of PHLPP in colorectal cancer. In this study, we show that the deubiquitinase USP46 stabilizes the expression of both PHLPP isoforms by reducing the rate of PHLPP degradation. USP46 binds to PHLPP and directly removes the polyubiquitin chains from PHLPP
in vitro
and in cells. Increased USP46 expression correlates with decreased ubiquitination and upregulation of PHLPP proteins in colon cancer cells, whereas knockdown of USP46 has the opposite effect. Functionally, USP46-mediated stabilization of PHLPP and the subsequent inhibition of Akt result in a decrease in cell proliferation and tumorigenesis of colon cancer cells
in vivo
. Moreover, reduced USP46 protein level is found associated with poor PHLPP expression in colorectal cancer patient specimens. Taken together, these results indentify a tumor suppressor role of USP46 in promoting PHLPP expression and inhibiting Akt signaling in colon cancer.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/onc.2012.66</identifier><identifier>PMID: 22391563</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/45/474/582 ; 631/67/581 ; 631/80/86 ; 692/699/67/1504/1885/1393 ; AKT protein ; Animals ; Apoptosis ; Cell Biology ; Cell Line, Tumor ; Cell Proliferation ; Cell Transformation, Neoplastic - genetics ; Cell Transformation, Neoplastic - metabolism ; Colon cancer ; Colonic Neoplasms - enzymology ; Colonic Neoplasms - genetics ; Colonic Neoplasms - metabolism ; Colorectal cancer ; Development and progression ; Endopeptidases - genetics ; Endopeptidases - metabolism ; Enzymes ; Genes, Tumor Suppressor ; Genetic aspects ; HCT116 Cells ; HEK293 Cells ; Human Genetics ; Humans ; Internal Medicine ; Male ; Medicine ; Medicine & Public Health ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Oncology ; original-article ; Phosphatases ; Phosphoprotein Phosphatases - genetics ; Phosphoprotein Phosphatases - metabolism ; Physiological aspects ; proteasomes ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Isoforms ; protein phosphatase ; Proteins ; Proto-Oncogene Proteins c-akt - genetics ; Proto-Oncogene Proteins c-akt - metabolism ; Signal Transduction ; Tumor suppressor genes ; Tumorigenesis ; Ubiquitin ; Ubiquitin-proteasome system ; Ubiquitination ; Up-Regulation</subject><ispartof>Oncogene, 2013-01, Vol.32 (4), p.471-478</ispartof><rights>Macmillan Publishers Limited 2013</rights><rights>COPYRIGHT 2013 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jan 24, 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c546t-299ae190881b21b0186b33aa931cefcc8b4ae4387053a56e5cc505c4fe761c4d3</citedby><cites>FETCH-LOGICAL-c546t-299ae190881b21b0186b33aa931cefcc8b4ae4387053a56e5cc505c4fe761c4d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/onc.2012.66$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/onc.2012.66$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22391563$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, X</creatorcontrib><creatorcontrib>Stevens, P D</creatorcontrib><creatorcontrib>Yang, H</creatorcontrib><creatorcontrib>Gulhati, P</creatorcontrib><creatorcontrib>Wang, W</creatorcontrib><creatorcontrib>Evers, B M</creatorcontrib><creatorcontrib>Gao, T</creatorcontrib><title>The deubiquitination enzyme USP46 functions as a tumor suppressor by controlling PHLPP-dependent attenuation of Akt signaling in colon cancer</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>PH domain leucine-rich-repeats protein phosphatase (PHLPP) is a family of Ser/Thr protein phosphatases that serve as tumor suppressors by negatively regulating Akt. Our recent studies have demonstrated that the ubiquitin proteasome pathway has an important role in the downregulation of PHLPP in colorectal cancer. In this study, we show that the deubiquitinase USP46 stabilizes the expression of both PHLPP isoforms by reducing the rate of PHLPP degradation. USP46 binds to PHLPP and directly removes the polyubiquitin chains from PHLPP
in vitro
and in cells. Increased USP46 expression correlates with decreased ubiquitination and upregulation of PHLPP proteins in colon cancer cells, whereas knockdown of USP46 has the opposite effect. Functionally, USP46-mediated stabilization of PHLPP and the subsequent inhibition of Akt result in a decrease in cell proliferation and tumorigenesis of colon cancer cells
in vivo
. Moreover, reduced USP46 protein level is found associated with poor PHLPP expression in colorectal cancer patient specimens. Taken together, these results indentify a tumor suppressor role of USP46 in promoting PHLPP expression and inhibiting Akt signaling in colon cancer.</description><subject>631/45/474/582</subject><subject>631/67/581</subject><subject>631/80/86</subject><subject>692/699/67/1504/1885/1393</subject><subject>AKT protein</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Cell Biology</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>Cell Transformation, Neoplastic - metabolism</subject><subject>Colon cancer</subject><subject>Colonic Neoplasms - enzymology</subject><subject>Colonic Neoplasms - genetics</subject><subject>Colonic Neoplasms - metabolism</subject><subject>Colorectal cancer</subject><subject>Development and progression</subject><subject>Endopeptidases - genetics</subject><subject>Endopeptidases - metabolism</subject><subject>Enzymes</subject><subject>Genes, Tumor Suppressor</subject><subject>Genetic aspects</subject><subject>HCT116 Cells</subject><subject>HEK293 Cells</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Oncology</subject><subject>original-article</subject><subject>Phosphatases</subject><subject>Phosphoprotein Phosphatases - genetics</subject><subject>Phosphoprotein Phosphatases - metabolism</subject><subject>Physiological aspects</subject><subject>proteasomes</subject><subject>Protein Binding</subject><subject>Protein Interaction Domains and Motifs</subject><subject>Protein Isoforms</subject><subject>protein phosphatase</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-akt - genetics</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Signal Transduction</subject><subject>Tumor suppressor genes</subject><subject>Tumorigenesis</subject><subject>Ubiquitin</subject><subject>Ubiquitin-proteasome system</subject><subject>Ubiquitination</subject><subject>Up-Regulation</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptkt9r1TAUx4so7jp98l0Cvgjaa340afsyuAx1wgUvuD2HND3tMtukSxrh-j_4P5vuzrnJSCDhnM_5Jt_kZNlrgtcEs-qjs3pNMaFrIZ5kK1KUIue8Lp5mK1xznNeU0aPsRQhXGOOyxvR5dkQpqwkXbJX9Pr8E1EJszHU0s7FqNs4isL_2I6CL77tCoC5avUQDUmmiOY7OoxCnyUMIadvskXZ29m4YjO3R7my72-UtTGBbsDNS8ww2HnRdhzY_ZhRMb9UNbGyqHVJGK6vBv8yedWoI8Op2Pc4uPn86Pz3Lt9--fD3dbHPNCzHntK4VkBpXFWkoaTCpRMOYUjUjGjqtq6ZQULCqxJwpLoBrzTHXRQelILpo2XF2ctCdYjNCq9M9vRrk5M2o_F46ZeTDjDWXsnc_JWMlIUIkgXe3At5dRwizHE3QMAzKgotBElpxXBcclwl9-x965aJP_heqpIwxwcQ_qlcDSGM7l87Vi6jcMFKxRQonav0IlUYLo0mfAJ1J8QcF7w8F2rsQPHR3HgmWS_fI1D1y6R554-rN_We5Y_-2SwI-HICQUrYHf8_LI3p_AFEDz-E</recordid><startdate>20130124</startdate><enddate>20130124</enddate><creator>Li, X</creator><creator>Stevens, P D</creator><creator>Yang, H</creator><creator>Gulhati, P</creator><creator>Wang, W</creator><creator>Evers, B M</creator><creator>Gao, T</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>3V.</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20130124</creationdate><title>The deubiquitination enzyme USP46 functions as a tumor suppressor by controlling PHLPP-dependent attenuation of Akt signaling in colon cancer</title><author>Li, X ; Stevens, P D ; Yang, H ; Gulhati, P ; Wang, W ; Evers, B M ; Gao, T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c546t-299ae190881b21b0186b33aa931cefcc8b4ae4387053a56e5cc505c4fe761c4d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>631/45/474/582</topic><topic>631/67/581</topic><topic>631/80/86</topic><topic>692/699/67/1504/1885/1393</topic><topic>AKT protein</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Cell Biology</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Cell Transformation, Neoplastic - genetics</topic><topic>Cell Transformation, Neoplastic - metabolism</topic><topic>Colon cancer</topic><topic>Colonic Neoplasms - enzymology</topic><topic>Colonic Neoplasms - genetics</topic><topic>Colonic Neoplasms - metabolism</topic><topic>Colorectal cancer</topic><topic>Development and progression</topic><topic>Endopeptidases - genetics</topic><topic>Endopeptidases - metabolism</topic><topic>Enzymes</topic><topic>Genes, Tumor Suppressor</topic><topic>Genetic aspects</topic><topic>HCT116 Cells</topic><topic>HEK293 Cells</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Oncology</topic><topic>original-article</topic><topic>Phosphatases</topic><topic>Phosphoprotein Phosphatases - genetics</topic><topic>Phosphoprotein Phosphatases - metabolism</topic><topic>Physiological aspects</topic><topic>proteasomes</topic><topic>Protein Binding</topic><topic>Protein Interaction Domains and Motifs</topic><topic>Protein Isoforms</topic><topic>protein phosphatase</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-akt - genetics</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Signal Transduction</topic><topic>Tumor suppressor genes</topic><topic>Tumorigenesis</topic><topic>Ubiquitin</topic><topic>Ubiquitin-proteasome system</topic><topic>Ubiquitination</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, X</creatorcontrib><creatorcontrib>Stevens, P D</creatorcontrib><creatorcontrib>Yang, H</creatorcontrib><creatorcontrib>Gulhati, P</creatorcontrib><creatorcontrib>Wang, W</creatorcontrib><creatorcontrib>Evers, B M</creatorcontrib><creatorcontrib>Gao, T</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, X</au><au>Stevens, P D</au><au>Yang, H</au><au>Gulhati, P</au><au>Wang, W</au><au>Evers, B M</au><au>Gao, T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The deubiquitination enzyme USP46 functions as a tumor suppressor by controlling PHLPP-dependent attenuation of Akt signaling in colon cancer</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2013-01-24</date><risdate>2013</risdate><volume>32</volume><issue>4</issue><spage>471</spage><epage>478</epage><pages>471-478</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>PH domain leucine-rich-repeats protein phosphatase (PHLPP) is a family of Ser/Thr protein phosphatases that serve as tumor suppressors by negatively regulating Akt. Our recent studies have demonstrated that the ubiquitin proteasome pathway has an important role in the downregulation of PHLPP in colorectal cancer. In this study, we show that the deubiquitinase USP46 stabilizes the expression of both PHLPP isoforms by reducing the rate of PHLPP degradation. USP46 binds to PHLPP and directly removes the polyubiquitin chains from PHLPP
in vitro
and in cells. Increased USP46 expression correlates with decreased ubiquitination and upregulation of PHLPP proteins in colon cancer cells, whereas knockdown of USP46 has the opposite effect. Functionally, USP46-mediated stabilization of PHLPP and the subsequent inhibition of Akt result in a decrease in cell proliferation and tumorigenesis of colon cancer cells
in vivo
. Moreover, reduced USP46 protein level is found associated with poor PHLPP expression in colorectal cancer patient specimens. Taken together, these results indentify a tumor suppressor role of USP46 in promoting PHLPP expression and inhibiting Akt signaling in colon cancer.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>22391563</pmid><doi>10.1038/onc.2012.66</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0950-9232 |
| ispartof | Oncogene, 2013-01, Vol.32 (4), p.471-478 |
| issn | 0950-9232 1476-5594 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3371166 |
| source | MEDLINE; SpringerLink_现刊; Nature; EZB Electronic Journals Library |
| subjects | 631/45/474/582 631/67/581 631/80/86 692/699/67/1504/1885/1393 AKT protein Animals Apoptosis Cell Biology Cell Line, Tumor Cell Proliferation Cell Transformation, Neoplastic - genetics Cell Transformation, Neoplastic - metabolism Colon cancer Colonic Neoplasms - enzymology Colonic Neoplasms - genetics Colonic Neoplasms - metabolism Colorectal cancer Development and progression Endopeptidases - genetics Endopeptidases - metabolism Enzymes Genes, Tumor Suppressor Genetic aspects HCT116 Cells HEK293 Cells Human Genetics Humans Internal Medicine Male Medicine Medicine & Public Health Mice Mice, Inbred BALB C Mice, Nude Nuclear Proteins - genetics Nuclear Proteins - metabolism Oncology original-article Phosphatases Phosphoprotein Phosphatases - genetics Phosphoprotein Phosphatases - metabolism Physiological aspects proteasomes Protein Binding Protein Interaction Domains and Motifs Protein Isoforms protein phosphatase Proteins Proto-Oncogene Proteins c-akt - genetics Proto-Oncogene Proteins c-akt - metabolism Signal Transduction Tumor suppressor genes Tumorigenesis Ubiquitin Ubiquitin-proteasome system Ubiquitination Up-Regulation |
| title | The deubiquitination enzyme USP46 functions as a tumor suppressor by controlling PHLPP-dependent attenuation of Akt signaling in colon cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-03T15%3A24%3A31IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20deubiquitination%20enzyme%20USP46%20functions%20as%20a%20tumor%20suppressor%20by%20controlling%20PHLPP-dependent%20attenuation%20of%20Akt%20signaling%20in%20colon%20cancer&rft.jtitle=Oncogene&rft.au=Li,%20X&rft.date=2013-01-24&rft.volume=32&rft.issue=4&rft.spage=471&rft.epage=478&rft.pages=471-478&rft.issn=0950-9232&rft.eissn=1476-5594&rft.coden=ONCNES&rft_id=info:doi/10.1038/onc.2012.66&rft_dat=%3Cgale_pubme%3EA318345070%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1272333636&rft_id=info:pmid/22391563&rft_galeid=A318345070&rfr_iscdi=true |