O-GlcNAcylation regulation of RIPK1-dependent apoptosis dictates sensitivity to sunitinib in renal cell carcinoma
Receptor interacting protein kinase 1 (RIPK1) has emerged as a key regulatory molecule that influences the balance between cell death and cell survival. Under external stress, RIPK1 determines whether a cell undergoes RIPK-dependent apoptosis (RDA) or survives by activating NF-κB signaling. However,...
Gespeichert in:
| Veröffentlicht in: | Drug resistance updates 2024-11, Vol.77, p.101150, Article 101150 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | |
| container_start_page | 101150 |
| container_title | Drug resistance updates |
| container_volume | 77 |
| creator | Zeng, Xiangbo Chen, Zhiliang Zhu, Yuanchao Liu, Lei Zhang, Zhiyong Xiao, Yongyuan Wang, Qiong Pang, Shiyu Zhao, Fengjin Xu, Bihong Leng, Mengxin Liu, Xiaocen Hu, Chenxi Zeng, Siying Li, Fei Xie, Wenlian Tan, Wanlong Zheng, Zaosong |
| description | Receptor interacting protein kinase 1 (RIPK1) has emerged as a key regulatory molecule that influences the balance between cell death and cell survival. Under external stress, RIPK1 determines whether a cell undergoes RIPK-dependent apoptosis (RDA) or survives by activating NF-κB signaling. However, the role and mechanisms of RIPK1 on sunitinib sensitivity in renal cell carcinoma (RCC) remain elusive. In this study, we demonstrated that the O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) of RIPK1 induces sunitinib resistance in RCC by inhibiting RDA. O-GlcNAc transferase (OGT) specifically interacts with RIPK1 through its tetratricopeptide repeats (TPR) domain and facilitates RIPK1 O-GlcNAcylation. The O-GlcNAcylation of RIPK1 at Ser331, Ser440 and Ser669 regulates RIPK1 ubiquitination and the formation of the RIPK1/FADD/Caspase-8 complex, thereby inhibiting sunitinib-induced RDA in RCC. Site-specific depletion of O-GlcNAcylation on RIPK1 affects the formation of the RIPK1/FADD/Caspase 8 complex, leading to increased sunitinib sensitivity in RCC.
Our data highlight the significance of aberrant RIPK1 O-GlcNAcylation in the development of sunitinib resistance and indicate that targeting RIPK1 O-GlcNAcylation could be a promising therapeutic strategy for RCC. |
| doi_str_mv | 10.1016/j.drup.2024.101150 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3105490505</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1368764624001080</els_id><sourcerecordid>3105490505</sourcerecordid><originalsourceid>FETCH-LOGICAL-c237t-cc49b92ba3283e0bebdac0017d01545c65963111bf5d8968353930679e01bcc83</originalsourceid><addsrcrecordid>eNp9kE1v3CAQhlGVqknT_IEcKo65eMuHwUbKJYqaTdSoqarmjDDMRqy84ACOtP--WLvtMRcY0DOvZh6ELilZUULlt-3KpXlaMcLa5YMK8gGdUcFZw0jfntSay77pZCtP0eect6QyrVKf0ClXrJMd42fo9alZj_bnjd2PpvgYcIKX-VjGDf798OsHbRxMEByEgs0UpxKzz9h5W0yBjDOE7It_82WPS8R5DvUV_ID9EhbMiC2M9TDJ-hB35gv6uDFjhovjfY6e777_ub1vHp_WD7c3j41lvCuNta0aFBsMZz0HMsDgjK0bdI5Q0QorhZKcUjpshOuV7LngihPZKSB0sLbn5-jqkDul-DpDLnrn8zKKCRDnrDklolVEEFFRdkBtijkn2Ogp-Z1Je02JXlTrrV5U60W1PqiuTV-P-fOwA_e_5Z_bClwfAKhbvnlIOlsPwYLzCWzRLvr38v8CFvKQWA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3105490505</pqid></control><display><type>article</type><title>O-GlcNAcylation regulation of RIPK1-dependent apoptosis dictates sensitivity to sunitinib in renal cell carcinoma</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><creator>Zeng, Xiangbo ; Chen, Zhiliang ; Zhu, Yuanchao ; Liu, Lei ; Zhang, Zhiyong ; Xiao, Yongyuan ; Wang, Qiong ; Pang, Shiyu ; Zhao, Fengjin ; Xu, Bihong ; Leng, Mengxin ; Liu, Xiaocen ; Hu, Chenxi ; Zeng, Siying ; Li, Fei ; Xie, Wenlian ; Tan, Wanlong ; Zheng, Zaosong</creator><creatorcontrib>Zeng, Xiangbo ; Chen, Zhiliang ; Zhu, Yuanchao ; Liu, Lei ; Zhang, Zhiyong ; Xiao, Yongyuan ; Wang, Qiong ; Pang, Shiyu ; Zhao, Fengjin ; Xu, Bihong ; Leng, Mengxin ; Liu, Xiaocen ; Hu, Chenxi ; Zeng, Siying ; Li, Fei ; Xie, Wenlian ; Tan, Wanlong ; Zheng, Zaosong</creatorcontrib><description>Receptor interacting protein kinase 1 (RIPK1) has emerged as a key regulatory molecule that influences the balance between cell death and cell survival. Under external stress, RIPK1 determines whether a cell undergoes RIPK-dependent apoptosis (RDA) or survives by activating NF-κB signaling. However, the role and mechanisms of RIPK1 on sunitinib sensitivity in renal cell carcinoma (RCC) remain elusive. In this study, we demonstrated that the O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) of RIPK1 induces sunitinib resistance in RCC by inhibiting RDA. O-GlcNAc transferase (OGT) specifically interacts with RIPK1 through its tetratricopeptide repeats (TPR) domain and facilitates RIPK1 O-GlcNAcylation. The O-GlcNAcylation of RIPK1 at Ser331, Ser440 and Ser669 regulates RIPK1 ubiquitination and the formation of the RIPK1/FADD/Caspase-8 complex, thereby inhibiting sunitinib-induced RDA in RCC. Site-specific depletion of O-GlcNAcylation on RIPK1 affects the formation of the RIPK1/FADD/Caspase 8 complex, leading to increased sunitinib sensitivity in RCC.
Our data highlight the significance of aberrant RIPK1 O-GlcNAcylation in the development of sunitinib resistance and indicate that targeting RIPK1 O-GlcNAcylation could be a promising therapeutic strategy for RCC.</description><identifier>ISSN: 1368-7646</identifier><identifier>ISSN: 1532-2084</identifier><identifier>EISSN: 1532-2084</identifier><identifier>DOI: 10.1016/j.drup.2024.101150</identifier><identifier>PMID: 39276723</identifier><language>eng</language><publisher>Scotland: Elsevier Ltd</publisher><subject>Antineoplastic Agents - pharmacology ; Apoptosis - drug effects ; Carcinoma, Renal Cell - drug therapy ; Carcinoma, Renal Cell - metabolism ; Carcinoma, Renal Cell - pathology ; Cell Line, Tumor ; Drug Resistance, Neoplasm - drug effects ; Humans ; Kidney Neoplasms - drug therapy ; Kidney Neoplasms - metabolism ; Kidney Neoplasms - pathology ; N-Acetylglucosaminyltransferases - metabolism ; O-GlcNAcylation ; OGT ; Receptor-Interacting Protein Serine-Threonine Kinases - metabolism ; renal cell carcinoma ; RIPK1 ; Signal Transduction - drug effects ; Sunitinib ; Sunitinib - pharmacology ; Ubiquitination - drug effects</subject><ispartof>Drug resistance updates, 2024-11, Vol.77, p.101150, Article 101150</ispartof><rights>2024 Elsevier Ltd</rights><rights>Copyright © 2024 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c237t-cc49b92ba3283e0bebdac0017d01545c65963111bf5d8968353930679e01bcc83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.drup.2024.101150$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39276723$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zeng, Xiangbo</creatorcontrib><creatorcontrib>Chen, Zhiliang</creatorcontrib><creatorcontrib>Zhu, Yuanchao</creatorcontrib><creatorcontrib>Liu, Lei</creatorcontrib><creatorcontrib>Zhang, Zhiyong</creatorcontrib><creatorcontrib>Xiao, Yongyuan</creatorcontrib><creatorcontrib>Wang, Qiong</creatorcontrib><creatorcontrib>Pang, Shiyu</creatorcontrib><creatorcontrib>Zhao, Fengjin</creatorcontrib><creatorcontrib>Xu, Bihong</creatorcontrib><creatorcontrib>Leng, Mengxin</creatorcontrib><creatorcontrib>Liu, Xiaocen</creatorcontrib><creatorcontrib>Hu, Chenxi</creatorcontrib><creatorcontrib>Zeng, Siying</creatorcontrib><creatorcontrib>Li, Fei</creatorcontrib><creatorcontrib>Xie, Wenlian</creatorcontrib><creatorcontrib>Tan, Wanlong</creatorcontrib><creatorcontrib>Zheng, Zaosong</creatorcontrib><title>O-GlcNAcylation regulation of RIPK1-dependent apoptosis dictates sensitivity to sunitinib in renal cell carcinoma</title><title>Drug resistance updates</title><addtitle>Drug Resist Updat</addtitle><description>Receptor interacting protein kinase 1 (RIPK1) has emerged as a key regulatory molecule that influences the balance between cell death and cell survival. Under external stress, RIPK1 determines whether a cell undergoes RIPK-dependent apoptosis (RDA) or survives by activating NF-κB signaling. However, the role and mechanisms of RIPK1 on sunitinib sensitivity in renal cell carcinoma (RCC) remain elusive. In this study, we demonstrated that the O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) of RIPK1 induces sunitinib resistance in RCC by inhibiting RDA. O-GlcNAc transferase (OGT) specifically interacts with RIPK1 through its tetratricopeptide repeats (TPR) domain and facilitates RIPK1 O-GlcNAcylation. The O-GlcNAcylation of RIPK1 at Ser331, Ser440 and Ser669 regulates RIPK1 ubiquitination and the formation of the RIPK1/FADD/Caspase-8 complex, thereby inhibiting sunitinib-induced RDA in RCC. Site-specific depletion of O-GlcNAcylation on RIPK1 affects the formation of the RIPK1/FADD/Caspase 8 complex, leading to increased sunitinib sensitivity in RCC.
Our data highlight the significance of aberrant RIPK1 O-GlcNAcylation in the development of sunitinib resistance and indicate that targeting RIPK1 O-GlcNAcylation could be a promising therapeutic strategy for RCC.</description><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Carcinoma, Renal Cell - drug therapy</subject><subject>Carcinoma, Renal Cell - metabolism</subject><subject>Carcinoma, Renal Cell - pathology</subject><subject>Cell Line, Tumor</subject><subject>Drug Resistance, Neoplasm - drug effects</subject><subject>Humans</subject><subject>Kidney Neoplasms - drug therapy</subject><subject>Kidney Neoplasms - metabolism</subject><subject>Kidney Neoplasms - pathology</subject><subject>N-Acetylglucosaminyltransferases - metabolism</subject><subject>O-GlcNAcylation</subject><subject>OGT</subject><subject>Receptor-Interacting Protein Serine-Threonine Kinases - metabolism</subject><subject>renal cell carcinoma</subject><subject>RIPK1</subject><subject>Signal Transduction - drug effects</subject><subject>Sunitinib</subject><subject>Sunitinib - pharmacology</subject><subject>Ubiquitination - drug effects</subject><issn>1368-7646</issn><issn>1532-2084</issn><issn>1532-2084</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1v3CAQhlGVqknT_IEcKo65eMuHwUbKJYqaTdSoqarmjDDMRqy84ACOtP--WLvtMRcY0DOvZh6ELilZUULlt-3KpXlaMcLa5YMK8gGdUcFZw0jfntSay77pZCtP0eect6QyrVKf0ClXrJMd42fo9alZj_bnjd2PpvgYcIKX-VjGDf798OsHbRxMEByEgs0UpxKzz9h5W0yBjDOE7It_82WPS8R5DvUV_ID9EhbMiC2M9TDJ-hB35gv6uDFjhovjfY6e777_ub1vHp_WD7c3j41lvCuNta0aFBsMZz0HMsDgjK0bdI5Q0QorhZKcUjpshOuV7LngihPZKSB0sLbn5-jqkDul-DpDLnrn8zKKCRDnrDklolVEEFFRdkBtijkn2Ogp-Z1Je02JXlTrrV5U60W1PqiuTV-P-fOwA_e_5Z_bClwfAKhbvnlIOlsPwYLzCWzRLvr38v8CFvKQWA</recordid><startdate>202411</startdate><enddate>202411</enddate><creator>Zeng, Xiangbo</creator><creator>Chen, Zhiliang</creator><creator>Zhu, Yuanchao</creator><creator>Liu, Lei</creator><creator>Zhang, Zhiyong</creator><creator>Xiao, Yongyuan</creator><creator>Wang, Qiong</creator><creator>Pang, Shiyu</creator><creator>Zhao, Fengjin</creator><creator>Xu, Bihong</creator><creator>Leng, Mengxin</creator><creator>Liu, Xiaocen</creator><creator>Hu, Chenxi</creator><creator>Zeng, Siying</creator><creator>Li, Fei</creator><creator>Xie, Wenlian</creator><creator>Tan, Wanlong</creator><creator>Zheng, Zaosong</creator><general>Elsevier Ltd</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></search><sort><creationdate>202411</creationdate><title>O-GlcNAcylation regulation of RIPK1-dependent apoptosis dictates sensitivity to sunitinib in renal cell carcinoma</title><author>Zeng, Xiangbo ; Chen, Zhiliang ; Zhu, Yuanchao ; Liu, Lei ; Zhang, Zhiyong ; Xiao, Yongyuan ; Wang, Qiong ; Pang, Shiyu ; Zhao, Fengjin ; Xu, Bihong ; Leng, Mengxin ; Liu, Xiaocen ; Hu, Chenxi ; Zeng, Siying ; Li, Fei ; Xie, Wenlian ; Tan, Wanlong ; Zheng, Zaosong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c237t-cc49b92ba3283e0bebdac0017d01545c65963111bf5d8968353930679e01bcc83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>Carcinoma, Renal Cell - drug therapy</topic><topic>Carcinoma, Renal Cell - metabolism</topic><topic>Carcinoma, Renal Cell - pathology</topic><topic>Cell Line, Tumor</topic><topic>Drug Resistance, Neoplasm - drug effects</topic><topic>Humans</topic><topic>Kidney Neoplasms - drug therapy</topic><topic>Kidney Neoplasms - metabolism</topic><topic>Kidney Neoplasms - pathology</topic><topic>N-Acetylglucosaminyltransferases - metabolism</topic><topic>O-GlcNAcylation</topic><topic>OGT</topic><topic>Receptor-Interacting Protein Serine-Threonine Kinases - metabolism</topic><topic>renal cell carcinoma</topic><topic>RIPK1</topic><topic>Signal Transduction - drug effects</topic><topic>Sunitinib</topic><topic>Sunitinib - pharmacology</topic><topic>Ubiquitination - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zeng, Xiangbo</creatorcontrib><creatorcontrib>Chen, Zhiliang</creatorcontrib><creatorcontrib>Zhu, Yuanchao</creatorcontrib><creatorcontrib>Liu, Lei</creatorcontrib><creatorcontrib>Zhang, Zhiyong</creatorcontrib><creatorcontrib>Xiao, Yongyuan</creatorcontrib><creatorcontrib>Wang, Qiong</creatorcontrib><creatorcontrib>Pang, Shiyu</creatorcontrib><creatorcontrib>Zhao, Fengjin</creatorcontrib><creatorcontrib>Xu, Bihong</creatorcontrib><creatorcontrib>Leng, Mengxin</creatorcontrib><creatorcontrib>Liu, Xiaocen</creatorcontrib><creatorcontrib>Hu, Chenxi</creatorcontrib><creatorcontrib>Zeng, Siying</creatorcontrib><creatorcontrib>Li, Fei</creatorcontrib><creatorcontrib>Xie, Wenlian</creatorcontrib><creatorcontrib>Tan, Wanlong</creatorcontrib><creatorcontrib>Zheng, Zaosong</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><jtitle>Drug resistance updates</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zeng, Xiangbo</au><au>Chen, Zhiliang</au><au>Zhu, Yuanchao</au><au>Liu, Lei</au><au>Zhang, Zhiyong</au><au>Xiao, Yongyuan</au><au>Wang, Qiong</au><au>Pang, Shiyu</au><au>Zhao, Fengjin</au><au>Xu, Bihong</au><au>Leng, Mengxin</au><au>Liu, Xiaocen</au><au>Hu, Chenxi</au><au>Zeng, Siying</au><au>Li, Fei</au><au>Xie, Wenlian</au><au>Tan, Wanlong</au><au>Zheng, Zaosong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>O-GlcNAcylation regulation of RIPK1-dependent apoptosis dictates sensitivity to sunitinib in renal cell carcinoma</atitle><jtitle>Drug resistance updates</jtitle><addtitle>Drug Resist Updat</addtitle><date>2024-11</date><risdate>2024</risdate><volume>77</volume><spage>101150</spage><pages>101150-</pages><artnum>101150</artnum><issn>1368-7646</issn><issn>1532-2084</issn><eissn>1532-2084</eissn><abstract>Receptor interacting protein kinase 1 (RIPK1) has emerged as a key regulatory molecule that influences the balance between cell death and cell survival. Under external stress, RIPK1 determines whether a cell undergoes RIPK-dependent apoptosis (RDA) or survives by activating NF-κB signaling. However, the role and mechanisms of RIPK1 on sunitinib sensitivity in renal cell carcinoma (RCC) remain elusive. In this study, we demonstrated that the O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) of RIPK1 induces sunitinib resistance in RCC by inhibiting RDA. O-GlcNAc transferase (OGT) specifically interacts with RIPK1 through its tetratricopeptide repeats (TPR) domain and facilitates RIPK1 O-GlcNAcylation. The O-GlcNAcylation of RIPK1 at Ser331, Ser440 and Ser669 regulates RIPK1 ubiquitination and the formation of the RIPK1/FADD/Caspase-8 complex, thereby inhibiting sunitinib-induced RDA in RCC. Site-specific depletion of O-GlcNAcylation on RIPK1 affects the formation of the RIPK1/FADD/Caspase 8 complex, leading to increased sunitinib sensitivity in RCC.
Our data highlight the significance of aberrant RIPK1 O-GlcNAcylation in the development of sunitinib resistance and indicate that targeting RIPK1 O-GlcNAcylation could be a promising therapeutic strategy for RCC.</abstract><cop>Scotland</cop><pub>Elsevier Ltd</pub><pmid>39276723</pmid><doi>10.1016/j.drup.2024.101150</doi></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1368-7646 |
| ispartof | Drug resistance updates, 2024-11, Vol.77, p.101150, Article 101150 |
| issn | 1368-7646 1532-2084 1532-2084 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_3105490505 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Antineoplastic Agents - pharmacology Apoptosis - drug effects Carcinoma, Renal Cell - drug therapy Carcinoma, Renal Cell - metabolism Carcinoma, Renal Cell - pathology Cell Line, Tumor Drug Resistance, Neoplasm - drug effects Humans Kidney Neoplasms - drug therapy Kidney Neoplasms - metabolism Kidney Neoplasms - pathology N-Acetylglucosaminyltransferases - metabolism O-GlcNAcylation OGT Receptor-Interacting Protein Serine-Threonine Kinases - metabolism renal cell carcinoma RIPK1 Signal Transduction - drug effects Sunitinib Sunitinib - pharmacology Ubiquitination - drug effects |
| title | O-GlcNAcylation regulation of RIPK1-dependent apoptosis dictates sensitivity to sunitinib in renal cell carcinoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T04%3A49%3A10IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=O-GlcNAcylation%20regulation%20of%20RIPK1-dependent%20apoptosis%20dictates%20sensitivity%20to%20sunitinib%20in%20renal%20cell%20carcinoma&rft.jtitle=Drug%20resistance%20updates&rft.au=Zeng,%20Xiangbo&rft.date=2024-11&rft.volume=77&rft.spage=101150&rft.pages=101150-&rft.artnum=101150&rft.issn=1368-7646&rft.eissn=1532-2084&rft_id=info:doi/10.1016/j.drup.2024.101150&rft_dat=%3Cproquest_cross%3E3105490505%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3105490505&rft_id=info:pmid/39276723&rft_els_id=S1368764624001080&rfr_iscdi=true |