CUL4B protects kidneys from acute injury by restraining p53/PAI-1 signaling
Acute kidney injury (AKI) caused by nephrotoxins, ischemia reperfusion (IR) or sepsis is associated with high morbidity and mortality. Unveiling new mechanisms underlying AKI can help develop new therapeutic strategy. Cullin 4B (CUL4B) is a scaffold protein in the CUL4B-RING E3 ubiquitin ligase (CRL...
Gespeichert in:
| Veröffentlicht in: | Cell death & disease 2024-12, Vol.15 (12), p.915-12, Article 915 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 12 |
|---|---|
| container_issue | 12 |
| container_start_page | 915 |
| container_title | Cell death & disease |
| container_volume | 15 |
| creator | Liu, Kaixuan Hao, Xiaoyu Gao, Yangfan Cao, Zhiyuan Hou, Min Qin, Lining Song, Yu Wang, Molin Jiang, Baichun Liu, Qiao Zou, Yongxin Gong, Yaoqin Liu, Guangyi Sun, Gongping |
| description | Acute kidney injury (AKI) caused by nephrotoxins, ischemia reperfusion (IR) or sepsis is associated with high morbidity and mortality. Unveiling new mechanisms underlying AKI can help develop new therapeutic strategy. Cullin 4B (CUL4B) is a scaffold protein in the CUL4B-RING E3 ubiquitin ligase (CRL4B) complex. Here, we demonstrate that CUL4B can protect kidneys from acute injury induced by cisplatin and IR. CUL4B is upregulated in mouse tubular epithelial cells (TECs) after cisplatin treatment or IR. Loss of CUL4B in kidneys exacerbates renal injury, inflammation, and apoptosis of TECs caused by cisplatin and IR. Transcriptome analysis reveals that
Cul4b
deficiency enhances injury-induced PAI-1 expression. CUL4B suppresses PAI-1 expression by promoting polyubiquitination and degradation of p53. Inhibition of either PAI-1 or p53 can prevent the aggravated renal injury and inflammation caused by loss of CUL4B. Our work has identified the kidney-protective role of CUL4B against acute injury. |
| doi_str_mv | 10.1038/s41419-024-07299-w |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11655551</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_e48021784eef4243802c22e0b5409377</doaj_id><sourcerecordid>3147129664</sourcerecordid><originalsourceid>FETCH-LOGICAL-c378t-7482b8568b23755aa6c7656aa08b7c819726dd90cbc2c99060e5ecf43d3b76d13</originalsourceid><addsrcrecordid>eNp9kctu1DAUhi0EolXpC7BAltiwCfX9skJlxGXESLCga8txnOAhYw920mreHndSSssCb2wff-f3OecH4CVGbzGi6qIwzLBuEGENkkTr5uYJOCWI4YYppZ8-OJ-A81K2qC5KEeHiOTihWmiOOT0FX1ZXG_Ye7nOavJsK_Bm66A8F9jntoHXz5GGI2zkfYHuA2Zcp2xBDHOCe04tvl-sGwxKGaMcaewGe9XYs_vxuPwNXHz98X31uNl8_rVeXm8ZRqaZGMkVaxYVqCZWcWyucFFxYi1QrncJaEtF1GrnWEac1Eshz73pGO9pK0WF6BtaLbpfs1uxz2Nl8MMkGcwykPBibp-BGbzxTiGCpmPc9I4zWmyPEo5YzpKmUVevdorWf253vnI-1w_GR6OOXGH6YIV0bjAWv67aaN3cKOf2a64TMLhTnx9FGn-ZiKGYSEy0Eq-jrf9BtmnMd3pGqBOGSVooslMuplOz7-2owMrfem8V7U703R-_NTU169bCP-5Q_TleALkCpT3Hw-e_f_5H9DZVct5I</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3146642573</pqid></control><display><type>article</type><title>CUL4B protects kidneys from acute injury by restraining p53/PAI-1 signaling</title><source>MEDLINE</source><source>Nature Free</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Springer Nature OA Free Journals</source><creator>Liu, Kaixuan ; Hao, Xiaoyu ; Gao, Yangfan ; Cao, Zhiyuan ; Hou, Min ; Qin, Lining ; Song, Yu ; Wang, Molin ; Jiang, Baichun ; Liu, Qiao ; Zou, Yongxin ; Gong, Yaoqin ; Liu, Guangyi ; Sun, Gongping</creator><creatorcontrib>Liu, Kaixuan ; Hao, Xiaoyu ; Gao, Yangfan ; Cao, Zhiyuan ; Hou, Min ; Qin, Lining ; Song, Yu ; Wang, Molin ; Jiang, Baichun ; Liu, Qiao ; Zou, Yongxin ; Gong, Yaoqin ; Liu, Guangyi ; Sun, Gongping</creatorcontrib><description>Acute kidney injury (AKI) caused by nephrotoxins, ischemia reperfusion (IR) or sepsis is associated with high morbidity and mortality. Unveiling new mechanisms underlying AKI can help develop new therapeutic strategy. Cullin 4B (CUL4B) is a scaffold protein in the CUL4B-RING E3 ubiquitin ligase (CRL4B) complex. Here, we demonstrate that CUL4B can protect kidneys from acute injury induced by cisplatin and IR. CUL4B is upregulated in mouse tubular epithelial cells (TECs) after cisplatin treatment or IR. Loss of CUL4B in kidneys exacerbates renal injury, inflammation, and apoptosis of TECs caused by cisplatin and IR. Transcriptome analysis reveals that
Cul4b
deficiency enhances injury-induced PAI-1 expression. CUL4B suppresses PAI-1 expression by promoting polyubiquitination and degradation of p53. Inhibition of either PAI-1 or p53 can prevent the aggravated renal injury and inflammation caused by loss of CUL4B. Our work has identified the kidney-protective role of CUL4B against acute injury.</description><identifier>ISSN: 2041-4889</identifier><identifier>EISSN: 2041-4889</identifier><identifier>DOI: 10.1038/s41419-024-07299-w</identifier><identifier>PMID: 39695153</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 13/1 ; 13/106 ; 13/2 ; 13/31 ; 13/51 ; 38 ; 38/109 ; 38/91 ; 631/80/82 ; 692/699/1585/4 ; 82 ; Acute Kidney Injury - metabolism ; Acute Kidney Injury - pathology ; Acute Kidney Injury - prevention & control ; Animals ; Antibodies ; Apoptosis ; Apoptosis - drug effects ; Biochemistry ; Biomedical and Life Sciences ; Cancer ; Cell Biology ; Cell Culture ; Cell death ; Cisplatin ; Cisplatin - pharmacology ; Creatinine ; Cullin ; Cullin Proteins - metabolism ; Epithelial cells ; Epithelial Cells - drug effects ; Epithelial Cells - metabolism ; Genes ; Humans ; Immunohistochemistry ; Immunology ; Inflammation ; Ischemia ; Kidney - drug effects ; Kidney - metabolism ; Kidney - pathology ; Kidneys ; Life Sciences ; Male ; Medicine ; Mice ; Mice, Inbred C57BL ; Morbidity ; Mortality ; p53 Protein ; Plasminogen Activator Inhibitor 1 - genetics ; Plasminogen Activator Inhibitor 1 - metabolism ; Proteins ; Reperfusion ; Reperfusion Injury - metabolism ; Reperfusion Injury - pathology ; Sepsis ; Serpin E2 ; Signal Transduction ; Transcriptomes ; Tumor Suppressor Protein p53 - metabolism ; Ubiquitin-protein ligase ; Ubiquitination</subject><ispartof>Cell death & disease, 2024-12, Vol.15 (12), p.915-12, Article 915</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>Copyright Springer Nature B.V. Dec 2024</rights><rights>The Author(s) 2024 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c378t-7482b8568b23755aa6c7656aa08b7c819726dd90cbc2c99060e5ecf43d3b76d13</cites><orcidid>0000-0001-5220-1638 ; 0000-0002-0411-2697 ; 0000-0001-6871-1560 ; 0000-0002-9150-7928 ; 0000-0003-4836-3954 ; 0000-0002-2886-9301</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655551/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655551/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,27903,27904,41099,42168,51554,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39695153$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Kaixuan</creatorcontrib><creatorcontrib>Hao, Xiaoyu</creatorcontrib><creatorcontrib>Gao, Yangfan</creatorcontrib><creatorcontrib>Cao, Zhiyuan</creatorcontrib><creatorcontrib>Hou, Min</creatorcontrib><creatorcontrib>Qin, Lining</creatorcontrib><creatorcontrib>Song, Yu</creatorcontrib><creatorcontrib>Wang, Molin</creatorcontrib><creatorcontrib>Jiang, Baichun</creatorcontrib><creatorcontrib>Liu, Qiao</creatorcontrib><creatorcontrib>Zou, Yongxin</creatorcontrib><creatorcontrib>Gong, Yaoqin</creatorcontrib><creatorcontrib>Liu, Guangyi</creatorcontrib><creatorcontrib>Sun, Gongping</creatorcontrib><title>CUL4B protects kidneys from acute injury by restraining p53/PAI-1 signaling</title><title>Cell death & disease</title><addtitle>Cell Death Dis</addtitle><addtitle>Cell Death Dis</addtitle><description>Acute kidney injury (AKI) caused by nephrotoxins, ischemia reperfusion (IR) or sepsis is associated with high morbidity and mortality. Unveiling new mechanisms underlying AKI can help develop new therapeutic strategy. Cullin 4B (CUL4B) is a scaffold protein in the CUL4B-RING E3 ubiquitin ligase (CRL4B) complex. Here, we demonstrate that CUL4B can protect kidneys from acute injury induced by cisplatin and IR. CUL4B is upregulated in mouse tubular epithelial cells (TECs) after cisplatin treatment or IR. Loss of CUL4B in kidneys exacerbates renal injury, inflammation, and apoptosis of TECs caused by cisplatin and IR. Transcriptome analysis reveals that
Cul4b
deficiency enhances injury-induced PAI-1 expression. CUL4B suppresses PAI-1 expression by promoting polyubiquitination and degradation of p53. Inhibition of either PAI-1 or p53 can prevent the aggravated renal injury and inflammation caused by loss of CUL4B. Our work has identified the kidney-protective role of CUL4B against acute injury.</description><subject>13</subject><subject>13/1</subject><subject>13/106</subject><subject>13/2</subject><subject>13/31</subject><subject>13/51</subject><subject>38</subject><subject>38/109</subject><subject>38/91</subject><subject>631/80/82</subject><subject>692/699/1585/4</subject><subject>82</subject><subject>Acute Kidney Injury - metabolism</subject><subject>Acute Kidney Injury - pathology</subject><subject>Acute Kidney Injury - prevention & control</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Cancer</subject><subject>Cell Biology</subject><subject>Cell Culture</subject><subject>Cell death</subject><subject>Cisplatin</subject><subject>Cisplatin - pharmacology</subject><subject>Creatinine</subject><subject>Cullin</subject><subject>Cullin Proteins - metabolism</subject><subject>Epithelial cells</subject><subject>Epithelial Cells - drug effects</subject><subject>Epithelial Cells - metabolism</subject><subject>Genes</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Immunology</subject><subject>Inflammation</subject><subject>Ischemia</subject><subject>Kidney - drug effects</subject><subject>Kidney - metabolism</subject><subject>Kidney - pathology</subject><subject>Kidneys</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Morbidity</subject><subject>Mortality</subject><subject>p53 Protein</subject><subject>Plasminogen Activator Inhibitor 1 - genetics</subject><subject>Plasminogen Activator Inhibitor 1 - metabolism</subject><subject>Proteins</subject><subject>Reperfusion</subject><subject>Reperfusion Injury - metabolism</subject><subject>Reperfusion Injury - pathology</subject><subject>Sepsis</subject><subject>Serpin E2</subject><subject>Signal Transduction</subject><subject>Transcriptomes</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Ubiquitin-protein ligase</subject><subject>Ubiquitination</subject><issn>2041-4889</issn><issn>2041-4889</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNp9kctu1DAUhi0EolXpC7BAltiwCfX9skJlxGXESLCga8txnOAhYw920mreHndSSssCb2wff-f3OecH4CVGbzGi6qIwzLBuEGENkkTr5uYJOCWI4YYppZ8-OJ-A81K2qC5KEeHiOTihWmiOOT0FX1ZXG_Ye7nOavJsK_Bm66A8F9jntoHXz5GGI2zkfYHuA2Zcp2xBDHOCe04tvl-sGwxKGaMcaewGe9XYs_vxuPwNXHz98X31uNl8_rVeXm8ZRqaZGMkVaxYVqCZWcWyucFFxYi1QrncJaEtF1GrnWEac1Eshz73pGO9pK0WF6BtaLbpfs1uxz2Nl8MMkGcwykPBibp-BGbzxTiGCpmPc9I4zWmyPEo5YzpKmUVevdorWf253vnI-1w_GR6OOXGH6YIV0bjAWv67aaN3cKOf2a64TMLhTnx9FGn-ZiKGYSEy0Eq-jrf9BtmnMd3pGqBOGSVooslMuplOz7-2owMrfem8V7U703R-_NTU169bCP-5Q_TleALkCpT3Hw-e_f_5H9DZVct5I</recordid><startdate>20241218</startdate><enddate>20241218</enddate><creator>Liu, Kaixuan</creator><creator>Hao, Xiaoyu</creator><creator>Gao, Yangfan</creator><creator>Cao, Zhiyuan</creator><creator>Hou, Min</creator><creator>Qin, Lining</creator><creator>Song, Yu</creator><creator>Wang, Molin</creator><creator>Jiang, Baichun</creator><creator>Liu, Qiao</creator><creator>Zou, Yongxin</creator><creator>Gong, Yaoqin</creator><creator>Liu, Guangyi</creator><creator>Sun, Gongping</creator><general>Nature Publishing Group UK</general><general>Springer Nature B.V</general><general>Nature Publishing Group</general><scope>C6C</scope><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>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</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>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-5220-1638</orcidid><orcidid>https://orcid.org/0000-0002-0411-2697</orcidid><orcidid>https://orcid.org/0000-0001-6871-1560</orcidid><orcidid>https://orcid.org/0000-0002-9150-7928</orcidid><orcidid>https://orcid.org/0000-0003-4836-3954</orcidid><orcidid>https://orcid.org/0000-0002-2886-9301</orcidid></search><sort><creationdate>20241218</creationdate><title>CUL4B protects kidneys from acute injury by restraining p53/PAI-1 signaling</title><author>Liu, Kaixuan ; Hao, Xiaoyu ; Gao, Yangfan ; Cao, Zhiyuan ; Hou, Min ; Qin, Lining ; Song, Yu ; Wang, Molin ; Jiang, Baichun ; Liu, Qiao ; Zou, Yongxin ; Gong, Yaoqin ; Liu, Guangyi ; Sun, Gongping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-7482b8568b23755aa6c7656aa08b7c819726dd90cbc2c99060e5ecf43d3b76d13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>13</topic><topic>13/1</topic><topic>13/106</topic><topic>13/2</topic><topic>13/31</topic><topic>13/51</topic><topic>38</topic><topic>38/109</topic><topic>38/91</topic><topic>631/80/82</topic><topic>692/699/1585/4</topic><topic>82</topic><topic>Acute Kidney Injury - metabolism</topic><topic>Acute Kidney Injury - pathology</topic><topic>Acute Kidney Injury - prevention & control</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Cancer</topic><topic>Cell Biology</topic><topic>Cell Culture</topic><topic>Cell death</topic><topic>Cisplatin</topic><topic>Cisplatin - pharmacology</topic><topic>Creatinine</topic><topic>Cullin</topic><topic>Cullin Proteins - metabolism</topic><topic>Epithelial cells</topic><topic>Epithelial Cells - drug effects</topic><topic>Epithelial Cells - metabolism</topic><topic>Genes</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Immunology</topic><topic>Inflammation</topic><topic>Ischemia</topic><topic>Kidney - drug effects</topic><topic>Kidney - metabolism</topic><topic>Kidney - pathology</topic><topic>Kidneys</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Medicine</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Morbidity</topic><topic>Mortality</topic><topic>p53 Protein</topic><topic>Plasminogen Activator Inhibitor 1 - genetics</topic><topic>Plasminogen Activator Inhibitor 1 - metabolism</topic><topic>Proteins</topic><topic>Reperfusion</topic><topic>Reperfusion Injury - metabolism</topic><topic>Reperfusion Injury - pathology</topic><topic>Sepsis</topic><topic>Serpin E2</topic><topic>Signal Transduction</topic><topic>Transcriptomes</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Ubiquitin-protein ligase</topic><topic>Ubiquitination</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Kaixuan</creatorcontrib><creatorcontrib>Hao, Xiaoyu</creatorcontrib><creatorcontrib>Gao, Yangfan</creatorcontrib><creatorcontrib>Cao, Zhiyuan</creatorcontrib><creatorcontrib>Hou, Min</creatorcontrib><creatorcontrib>Qin, Lining</creatorcontrib><creatorcontrib>Song, Yu</creatorcontrib><creatorcontrib>Wang, Molin</creatorcontrib><creatorcontrib>Jiang, Baichun</creatorcontrib><creatorcontrib>Liu, Qiao</creatorcontrib><creatorcontrib>Zou, Yongxin</creatorcontrib><creatorcontrib>Gong, Yaoqin</creatorcontrib><creatorcontrib>Liu, Guangyi</creatorcontrib><creatorcontrib>Sun, Gongping</creatorcontrib><collection>Springer Nature OA Free Journals</collection><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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</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>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Cell death & disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Kaixuan</au><au>Hao, Xiaoyu</au><au>Gao, Yangfan</au><au>Cao, Zhiyuan</au><au>Hou, Min</au><au>Qin, Lining</au><au>Song, Yu</au><au>Wang, Molin</au><au>Jiang, Baichun</au><au>Liu, Qiao</au><au>Zou, Yongxin</au><au>Gong, Yaoqin</au><au>Liu, Guangyi</au><au>Sun, Gongping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CUL4B protects kidneys from acute injury by restraining p53/PAI-1 signaling</atitle><jtitle>Cell death & disease</jtitle><stitle>Cell Death Dis</stitle><addtitle>Cell Death Dis</addtitle><date>2024-12-18</date><risdate>2024</risdate><volume>15</volume><issue>12</issue><spage>915</spage><epage>12</epage><pages>915-12</pages><artnum>915</artnum><issn>2041-4889</issn><eissn>2041-4889</eissn><abstract>Acute kidney injury (AKI) caused by nephrotoxins, ischemia reperfusion (IR) or sepsis is associated with high morbidity and mortality. Unveiling new mechanisms underlying AKI can help develop new therapeutic strategy. Cullin 4B (CUL4B) is a scaffold protein in the CUL4B-RING E3 ubiquitin ligase (CRL4B) complex. Here, we demonstrate that CUL4B can protect kidneys from acute injury induced by cisplatin and IR. CUL4B is upregulated in mouse tubular epithelial cells (TECs) after cisplatin treatment or IR. Loss of CUL4B in kidneys exacerbates renal injury, inflammation, and apoptosis of TECs caused by cisplatin and IR. Transcriptome analysis reveals that
Cul4b
deficiency enhances injury-induced PAI-1 expression. CUL4B suppresses PAI-1 expression by promoting polyubiquitination and degradation of p53. Inhibition of either PAI-1 or p53 can prevent the aggravated renal injury and inflammation caused by loss of CUL4B. Our work has identified the kidney-protective role of CUL4B against acute injury.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>39695153</pmid><doi>10.1038/s41419-024-07299-w</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-5220-1638</orcidid><orcidid>https://orcid.org/0000-0002-0411-2697</orcidid><orcidid>https://orcid.org/0000-0001-6871-1560</orcidid><orcidid>https://orcid.org/0000-0002-9150-7928</orcidid><orcidid>https://orcid.org/0000-0003-4836-3954</orcidid><orcidid>https://orcid.org/0000-0002-2886-9301</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2041-4889 |
| ispartof | Cell death & disease, 2024-12, Vol.15 (12), p.915-12, Article 915 |
| issn | 2041-4889 2041-4889 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11655551 |
| source | MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Springer Nature OA Free Journals |
| subjects | 13 13/1 13/106 13/2 13/31 13/51 38 38/109 38/91 631/80/82 692/699/1585/4 82 Acute Kidney Injury - metabolism Acute Kidney Injury - pathology Acute Kidney Injury - prevention & control Animals Antibodies Apoptosis Apoptosis - drug effects Biochemistry Biomedical and Life Sciences Cancer Cell Biology Cell Culture Cell death Cisplatin Cisplatin - pharmacology Creatinine Cullin Cullin Proteins - metabolism Epithelial cells Epithelial Cells - drug effects Epithelial Cells - metabolism Genes Humans Immunohistochemistry Immunology Inflammation Ischemia Kidney - drug effects Kidney - metabolism Kidney - pathology Kidneys Life Sciences Male Medicine Mice Mice, Inbred C57BL Morbidity Mortality p53 Protein Plasminogen Activator Inhibitor 1 - genetics Plasminogen Activator Inhibitor 1 - metabolism Proteins Reperfusion Reperfusion Injury - metabolism Reperfusion Injury - pathology Sepsis Serpin E2 Signal Transduction Transcriptomes Tumor Suppressor Protein p53 - metabolism Ubiquitin-protein ligase Ubiquitination |
| title | CUL4B protects kidneys from acute injury by restraining p53/PAI-1 signaling |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T23%3A33%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=CUL4B%20protects%20kidneys%20from%20acute%20injury%20by%20restraining%20p53/PAI-1%20signaling&rft.jtitle=Cell%20death%20&%20disease&rft.au=Liu,%20Kaixuan&rft.date=2024-12-18&rft.volume=15&rft.issue=12&rft.spage=915&rft.epage=12&rft.pages=915-12&rft.artnum=915&rft.issn=2041-4889&rft.eissn=2041-4889&rft_id=info:doi/10.1038/s41419-024-07299-w&rft_dat=%3Cproquest_doaj_%3E3147129664%3C/proquest_doaj_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3146642573&rft_id=info:pmid/39695153&rft_doaj_id=oai_doaj_org_article_e48021784eef4243802c22e0b5409377&rfr_iscdi=true |