Fusicoccin‑A Targets Cancerous Inhibitor of Protein Phosphatase 2A by Stabilizing a C‑Terminal Interaction with 14-3‑3
The cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein found overexpressed in many types of cancer. CIP2A has been shown to stabilize oncoproteins such as cMYC by shielding them from PP2A-mediated dephosphorylation. Here we report that the penultimate residue Ser904 in the C-ter...
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| Veröffentlicht in: | ACS chemical biology 2022-11, Vol.17 (11), p.2972-2978 |
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| creator | Brink, Hendrik J. van Senten, Jeffrey R. De Vries-van Leeuwen, Ingrid J. da Costa Pereira, Daniel Piersma, Sander R. Jimenez, Connie R. Centorrino, Federica Ottmann, Christian Siderius, Marco Smit, Martine J. de Boer, Albertus H. |
| description | The cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein found overexpressed in many types of cancer. CIP2A has been shown to stabilize oncoproteins such as cMYC by shielding them from PP2A-mediated dephosphorylation. Here we report that the penultimate residue Ser904 in the C-terminus of CIP2A can be phosphorylated to create a binding site for the regulatory protein 14-3-3. We demonstrate that 14-3-3 is a new interaction partner of CIP2A. The 14-3-3/CIP2A C-terminal interaction complex can be targeted by the protein–protein interaction (PPI) stabilizer fusicoccin-A (FC-A), resulting in enhanced levels of phosphorylated Ser904. FC-A treatment of TNBC cells leads to the increased association of CIP2A with 14-3-3. We show that the composite interface between 14 and 3-3 and CIP2A’s C-terminus can be targeted by the PPI stabilizer FC-A, providing a new interface that could potentially be exploited to modulate CIP2A’s activity. |
| doi_str_mv | 10.1021/acschembio.2c00299 |
| format | Article |
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CIP2A has been shown to stabilize oncoproteins such as cMYC by shielding them from PP2A-mediated dephosphorylation. Here we report that the penultimate residue Ser904 in the C-terminus of CIP2A can be phosphorylated to create a binding site for the regulatory protein 14-3-3. We demonstrate that 14-3-3 is a new interaction partner of CIP2A. The 14-3-3/CIP2A C-terminal interaction complex can be targeted by the protein–protein interaction (PPI) stabilizer fusicoccin-A (FC-A), resulting in enhanced levels of phosphorylated Ser904. FC-A treatment of TNBC cells leads to the increased association of CIP2A with 14-3-3. We show that the composite interface between 14 and 3-3 and CIP2A’s C-terminus can be targeted by the PPI stabilizer FC-A, providing a new interface that could potentially be exploited to modulate CIP2A’s activity.</description><identifier>ISSN: 1554-8929</identifier><identifier>EISSN: 1554-8937</identifier><identifier>DOI: 10.1021/acschembio.2c00299</identifier><identifier>PMID: 36255265</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Autoantigens - metabolism ; Humans ; Intracellular Signaling Peptides and Proteins ; Letters ; Membrane Proteins - metabolism ; Neoplasms ; Protein Phosphatase 2 - metabolism</subject><ispartof>ACS chemical biology, 2022-11, Vol.17 (11), p.2972-2978</ispartof><rights>2022 The Authors. Published by American Chemical Society</rights><rights>2022 The Authors. 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Biol</addtitle><description>The cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein found overexpressed in many types of cancer. CIP2A has been shown to stabilize oncoproteins such as cMYC by shielding them from PP2A-mediated dephosphorylation. Here we report that the penultimate residue Ser904 in the C-terminus of CIP2A can be phosphorylated to create a binding site for the regulatory protein 14-3-3. We demonstrate that 14-3-3 is a new interaction partner of CIP2A. The 14-3-3/CIP2A C-terminal interaction complex can be targeted by the protein–protein interaction (PPI) stabilizer fusicoccin-A (FC-A), resulting in enhanced levels of phosphorylated Ser904. FC-A treatment of TNBC cells leads to the increased association of CIP2A with 14-3-3. We show that the composite interface between 14 and 3-3 and CIP2A’s C-terminus can be targeted by the PPI stabilizer FC-A, providing a new interface that could potentially be exploited to modulate CIP2A’s activity.</description><subject>Autoantigens - metabolism</subject><subject>Humans</subject><subject>Intracellular Signaling Peptides and Proteins</subject><subject>Letters</subject><subject>Membrane Proteins - metabolism</subject><subject>Neoplasms</subject><subject>Protein Phosphatase 2 - metabolism</subject><issn>1554-8929</issn><issn>1554-8937</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc9uEzEQxi0EoqXwAhyQj1w2-O8mviBFUUsrVaIS4WyNvU7W1a4dbC-oFQdegVfsk-AqIcCF04w03_eb0XwIvaZkRgmj78Bm27vR-DhjlhCm1BN0SqUUzULx-dNjz9QJepHzLSGCtwv1HJ3wlknJWnmKvl9M2dtorQ8PP34u8RrS1pWMVxCsS3HK-Cr03vgSE44bfJNicT7gmz7mXQ8FssNsic0d_lTA-MHf-7DFgFcVtnZp9AGGSigugS0-BvzNlx5T0fAq4C_Rsw0M2b061DP0-eJ8vbpsrj9-uFotrxsQgpYGNhKYkc5BpygYIS0w6ARRnHDeKeAGFkYwMIoIpkRHFRAxJ7aVpGWccn6G3u-5u8mMrrMulASD3iU_QrrTEbz-dxJ8r7fxq1btXCnFKuDtAZDil8nlokefrRsGCK7-SLM5k63kLXncxfZSm2LOyW2OayjRj7HpP7HpQ2zV9ObvA4-W3zlVwWwvqGZ9G6dU_5r_R_wF4jaqMQ</recordid><startdate>20221118</startdate><enddate>20221118</enddate><creator>Brink, Hendrik J.</creator><creator>van Senten, Jeffrey R.</creator><creator>De Vries-van Leeuwen, Ingrid J.</creator><creator>da Costa Pereira, Daniel</creator><creator>Piersma, Sander R.</creator><creator>Jimenez, Connie R.</creator><creator>Centorrino, Federica</creator><creator>Ottmann, Christian</creator><creator>Siderius, Marco</creator><creator>Smit, Martine J.</creator><creator>de Boer, Albertus H.</creator><general>American Chemical Society</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><orcidid>https://orcid.org/0000-0001-7315-0315</orcidid><orcidid>https://orcid.org/0000-0003-2713-0238</orcidid><orcidid>https://orcid.org/0000-0001-6074-4392</orcidid></search><sort><creationdate>20221118</creationdate><title>Fusicoccin‑A Targets Cancerous Inhibitor of Protein Phosphatase 2A by Stabilizing a C‑Terminal Interaction with 14-3‑3</title><author>Brink, Hendrik J. ; van Senten, Jeffrey R. ; De Vries-van Leeuwen, Ingrid J. ; da Costa Pereira, Daniel ; Piersma, Sander R. ; Jimenez, Connie R. ; Centorrino, Federica ; Ottmann, Christian ; Siderius, Marco ; Smit, Martine J. ; de Boer, Albertus H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a441t-af5a2b5eead91ab45ca2ad4093033d9a3ba8b42ab904294d19a0470c650623133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Autoantigens - metabolism</topic><topic>Humans</topic><topic>Intracellular Signaling Peptides and Proteins</topic><topic>Letters</topic><topic>Membrane Proteins - metabolism</topic><topic>Neoplasms</topic><topic>Protein Phosphatase 2 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brink, Hendrik J.</creatorcontrib><creatorcontrib>van Senten, Jeffrey R.</creatorcontrib><creatorcontrib>De Vries-van Leeuwen, Ingrid J.</creatorcontrib><creatorcontrib>da Costa Pereira, Daniel</creatorcontrib><creatorcontrib>Piersma, Sander R.</creatorcontrib><creatorcontrib>Jimenez, Connie R.</creatorcontrib><creatorcontrib>Centorrino, Federica</creatorcontrib><creatorcontrib>Ottmann, Christian</creatorcontrib><creatorcontrib>Siderius, Marco</creatorcontrib><creatorcontrib>Smit, Martine J.</creatorcontrib><creatorcontrib>de Boer, Albertus H.</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>ACS chemical biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Brink, Hendrik J.</au><au>van Senten, Jeffrey R.</au><au>De Vries-van Leeuwen, Ingrid J.</au><au>da Costa Pereira, Daniel</au><au>Piersma, Sander R.</au><au>Jimenez, Connie R.</au><au>Centorrino, Federica</au><au>Ottmann, Christian</au><au>Siderius, Marco</au><au>Smit, Martine J.</au><au>de Boer, Albertus H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fusicoccin‑A Targets Cancerous Inhibitor of Protein Phosphatase 2A by Stabilizing a C‑Terminal Interaction with 14-3‑3</atitle><jtitle>ACS chemical biology</jtitle><addtitle>ACS Chem. Biol</addtitle><date>2022-11-18</date><risdate>2022</risdate><volume>17</volume><issue>11</issue><spage>2972</spage><epage>2978</epage><pages>2972-2978</pages><issn>1554-8929</issn><eissn>1554-8937</eissn><abstract>The cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein found overexpressed in many types of cancer. CIP2A has been shown to stabilize oncoproteins such as cMYC by shielding them from PP2A-mediated dephosphorylation. Here we report that the penultimate residue Ser904 in the C-terminus of CIP2A can be phosphorylated to create a binding site for the regulatory protein 14-3-3. We demonstrate that 14-3-3 is a new interaction partner of CIP2A. The 14-3-3/CIP2A C-terminal interaction complex can be targeted by the protein–protein interaction (PPI) stabilizer fusicoccin-A (FC-A), resulting in enhanced levels of phosphorylated Ser904. FC-A treatment of TNBC cells leads to the increased association of CIP2A with 14-3-3. 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| source | MEDLINE; American Chemical Society Journals |
| subjects | Autoantigens - metabolism Humans Intracellular Signaling Peptides and Proteins Letters Membrane Proteins - metabolism Neoplasms Protein Phosphatase 2 - metabolism |
| title | Fusicoccin‑A Targets Cancerous Inhibitor of Protein Phosphatase 2A by Stabilizing a C‑Terminal Interaction with 14-3‑3 |
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