Oxidative stress–specific interaction between FANCD2 and FOXO3a
The molecular pathway by which Fanconi anemia (FA) proteins function in oxidative stress response has not been defined. Here we report the functional interaction of the FA protein Fanconi anemia complementation group D2 (FANCD2) and the forkhead transcription factor forkhead box O 3a (FOXO3a). FOXO3...
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| Veröffentlicht in: | Blood 2010-02, Vol.115 (8), p.1545-1548 |
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| creator | Li, Jie Du, Wei Maynard, Suzette Andreassen, Paul R. Pang, Qishen |
| description | The molecular pathway by which Fanconi anemia (FA) proteins function in oxidative stress response has not been defined. Here we report the functional interaction of the FA protein Fanconi anemia complementation group D2 (FANCD2) and the forkhead transcription factor forkhead box O 3a (FOXO3a). FOXO3a colocalized with FANCD2 foci in response to oxidative stress. The FANCD2-FOXO3a complex was not detected in cells deficient for the FA core complex component FANCA but could be restored in corrected cells. Consistent with this, a nonmonoubiquitinated FANCD2 mutant failed to bind FOXO3a. Although both mitomycin C and ionizing radiation induced FANCD2 monoubiquitination, neither could induce the association of FANCD2 and FOXO3a. Overexpression of FOXO3a reduced abnormal accumulation of reactive oxygen species, enhanced cellular resistance to oxidative stress, and increased antioxidant gene expression in corrected but not mutant FA-D2 cells. The novel oxidative stress response pathway identified in this study, in which FANCD2 and FOXO3a converge, probably contributes to cellular antioxidant defense. |
| doi_str_mv | 10.1182/blood-2009-07-234385 |
| format | Article |
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Here we report the functional interaction of the FA protein Fanconi anemia complementation group D2 (FANCD2) and the forkhead transcription factor forkhead box O 3a (FOXO3a). FOXO3a colocalized with FANCD2 foci in response to oxidative stress. The FANCD2-FOXO3a complex was not detected in cells deficient for the FA core complex component FANCA but could be restored in corrected cells. Consistent with this, a nonmonoubiquitinated FANCD2 mutant failed to bind FOXO3a. Although both mitomycin C and ionizing radiation induced FANCD2 monoubiquitination, neither could induce the association of FANCD2 and FOXO3a. Overexpression of FOXO3a reduced abnormal accumulation of reactive oxygen species, enhanced cellular resistance to oxidative stress, and increased antioxidant gene expression in corrected but not mutant FA-D2 cells. The novel oxidative stress response pathway identified in this study, in which FANCD2 and FOXO3a converge, probably contributes to cellular antioxidant defense.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2009-07-234385</identifier><identifier>PMID: 20040763</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Antioxidants - metabolism ; Biological and medical sciences ; Cell Line ; Fanconi Anemia Complementation Group D2 Protein - genetics ; Fanconi Anemia Complementation Group D2 Protein - metabolism ; Forkhead Box Protein O3 ; Forkhead Transcription Factors - genetics ; Forkhead Transcription Factors - metabolism ; Gene Expression Regulation ; Hematologic and hematopoietic diseases ; Hematopoiesis and Stem Cells ; Humans ; Medical sciences ; Mitomycin - pharmacology ; Mutation ; Nucleic Acid Synthesis Inhibitors - pharmacology ; Oxidative Stress ; Protein Binding - drug effects ; Protein Binding - genetics ; Protein Binding - radiation effects ; Radiation, Ionizing ; Reactive Oxygen Species - metabolism ; Ubiquitination - drug effects ; Ubiquitination - genetics ; Ubiquitination - radiation effects</subject><ispartof>Blood, 2010-02, Vol.115 (8), p.1545-1548</ispartof><rights>2010 American Society of Hematology</rights><rights>2015 INIST-CNRS</rights><rights>2010 by The American Society of Hematology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c558t-caedc16e898dd54983b2021f0be199c881d3782ff71e5afc19f15fca126e60123</citedby><cites>FETCH-LOGICAL-c558t-caedc16e898dd54983b2021f0be199c881d3782ff71e5afc19f15fca126e60123</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22452532$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20040763$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Jie</creatorcontrib><creatorcontrib>Du, Wei</creatorcontrib><creatorcontrib>Maynard, Suzette</creatorcontrib><creatorcontrib>Andreassen, Paul R.</creatorcontrib><creatorcontrib>Pang, Qishen</creatorcontrib><title>Oxidative stress–specific interaction between FANCD2 and FOXO3a</title><title>Blood</title><addtitle>Blood</addtitle><description>The molecular pathway by which Fanconi anemia (FA) proteins function in oxidative stress response has not been defined. Here we report the functional interaction of the FA protein Fanconi anemia complementation group D2 (FANCD2) and the forkhead transcription factor forkhead box O 3a (FOXO3a). FOXO3a colocalized with FANCD2 foci in response to oxidative stress. The FANCD2-FOXO3a complex was not detected in cells deficient for the FA core complex component FANCA but could be restored in corrected cells. Consistent with this, a nonmonoubiquitinated FANCD2 mutant failed to bind FOXO3a. Although both mitomycin C and ionizing radiation induced FANCD2 monoubiquitination, neither could induce the association of FANCD2 and FOXO3a. Overexpression of FOXO3a reduced abnormal accumulation of reactive oxygen species, enhanced cellular resistance to oxidative stress, and increased antioxidant gene expression in corrected but not mutant FA-D2 cells. The novel oxidative stress response pathway identified in this study, in which FANCD2 and FOXO3a converge, probably contributes to cellular antioxidant defense.</description><subject>Antioxidants - metabolism</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Fanconi Anemia Complementation Group D2 Protein - genetics</subject><subject>Fanconi Anemia Complementation Group D2 Protein - metabolism</subject><subject>Forkhead Box Protein O3</subject><subject>Forkhead Transcription Factors - genetics</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Gene Expression Regulation</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematopoiesis and Stem Cells</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Mitomycin - pharmacology</subject><subject>Mutation</subject><subject>Nucleic Acid Synthesis Inhibitors - pharmacology</subject><subject>Oxidative Stress</subject><subject>Protein Binding - drug effects</subject><subject>Protein Binding - genetics</subject><subject>Protein Binding - radiation effects</subject><subject>Radiation, Ionizing</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Ubiquitination - drug effects</subject><subject>Ubiquitination - genetics</subject><subject>Ubiquitination - radiation effects</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1OwzAQhS0EoqVwA4SyYRkY23HibJCqQgEJ0Q1I7CzHHoNRm1R2KLDjDtyQk5BSfjesZjHvvZn3EbJL4YBSyQ6radPYlAGUKRQp4xmXYo30qWAyBWCwTvoAkKdZWdAe2YrxHoBmnIlN0utcGRQ575Ph5Mlb3foFJrENGOPby2uco_HOm8TXLQZtWt_USYXtI2KdjIeXo2OW6Nom48nNhOttsuH0NOLO5xyQ6_HJ1egsvZicno-GF6kRQrap0WgNzVGW0lqRlZJXDBh1UCEtSyMltbyQzLmCotDO0NJR4YymLMccKOMDcrTKnT9Usy4L6zboqZoHP9PhWTXaq7-b2t-p22ahmORdV-gCslWACU2MAd23l4JaIlUfSNUSqYJCrZB2tr3fd79NXww7wf6nQEejpy7o2vj4o2OZYIL_KoAdpYXHoKLxWBu0PqBplW38_5-8A1YRlmY</recordid><startdate>20100225</startdate><enddate>20100225</enddate><creator>Li, Jie</creator><creator>Du, Wei</creator><creator>Maynard, Suzette</creator><creator>Andreassen, Paul R.</creator><creator>Pang, Qishen</creator><general>Elsevier Inc</general><general>Americain Society of Hematology</general><general>American Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</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>5PM</scope></search><sort><creationdate>20100225</creationdate><title>Oxidative stress–specific interaction between FANCD2 and FOXO3a</title><author>Li, Jie ; Du, Wei ; Maynard, Suzette ; Andreassen, Paul R. ; Pang, Qishen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c558t-caedc16e898dd54983b2021f0be199c881d3782ff71e5afc19f15fca126e60123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Antioxidants - metabolism</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>Fanconi Anemia Complementation Group D2 Protein - genetics</topic><topic>Fanconi Anemia Complementation Group D2 Protein - metabolism</topic><topic>Forkhead Box Protein O3</topic><topic>Forkhead Transcription Factors - genetics</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>Gene Expression Regulation</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hematopoiesis and Stem Cells</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Mitomycin - pharmacology</topic><topic>Mutation</topic><topic>Nucleic Acid Synthesis Inhibitors - pharmacology</topic><topic>Oxidative Stress</topic><topic>Protein Binding - drug effects</topic><topic>Protein Binding - genetics</topic><topic>Protein Binding - radiation effects</topic><topic>Radiation, Ionizing</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Ubiquitination - drug effects</topic><topic>Ubiquitination - genetics</topic><topic>Ubiquitination - radiation effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Jie</creatorcontrib><creatorcontrib>Du, Wei</creatorcontrib><creatorcontrib>Maynard, Suzette</creatorcontrib><creatorcontrib>Andreassen, Paul R.</creatorcontrib><creatorcontrib>Pang, Qishen</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Jie</au><au>Du, Wei</au><au>Maynard, Suzette</au><au>Andreassen, Paul R.</au><au>Pang, Qishen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Oxidative stress–specific interaction between FANCD2 and FOXO3a</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2010-02-25</date><risdate>2010</risdate><volume>115</volume><issue>8</issue><spage>1545</spage><epage>1548</epage><pages>1545-1548</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>The molecular pathway by which Fanconi anemia (FA) proteins function in oxidative stress response has not been defined. Here we report the functional interaction of the FA protein Fanconi anemia complementation group D2 (FANCD2) and the forkhead transcription factor forkhead box O 3a (FOXO3a). FOXO3a colocalized with FANCD2 foci in response to oxidative stress. The FANCD2-FOXO3a complex was not detected in cells deficient for the FA core complex component FANCA but could be restored in corrected cells. Consistent with this, a nonmonoubiquitinated FANCD2 mutant failed to bind FOXO3a. Although both mitomycin C and ionizing radiation induced FANCD2 monoubiquitination, neither could induce the association of FANCD2 and FOXO3a. Overexpression of FOXO3a reduced abnormal accumulation of reactive oxygen species, enhanced cellular resistance to oxidative stress, and increased antioxidant gene expression in corrected but not mutant FA-D2 cells. The novel oxidative stress response pathway identified in this study, in which FANCD2 and FOXO3a converge, probably contributes to cellular antioxidant defense.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>20040763</pmid><doi>10.1182/blood-2009-07-234385</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Antioxidants - metabolism Biological and medical sciences Cell Line Fanconi Anemia Complementation Group D2 Protein - genetics Fanconi Anemia Complementation Group D2 Protein - metabolism Forkhead Box Protein O3 Forkhead Transcription Factors - genetics Forkhead Transcription Factors - metabolism Gene Expression Regulation Hematologic and hematopoietic diseases Hematopoiesis and Stem Cells Humans Medical sciences Mitomycin - pharmacology Mutation Nucleic Acid Synthesis Inhibitors - pharmacology Oxidative Stress Protein Binding - drug effects Protein Binding - genetics Protein Binding - radiation effects Radiation, Ionizing Reactive Oxygen Species - metabolism Ubiquitination - drug effects Ubiquitination - genetics Ubiquitination - radiation effects |
| title | Oxidative stress–specific interaction between FANCD2 and FOXO3a |
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