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The role of Rak in the regulation of stability and function of BRCA1
BRCA1 is an important player in the DNA damage response signaling, and its deficiency results in genomic instability. A complete loss or significantly reduced BRCA1 protein expression is often found in sporadic breast cancer cases despite the absence of genetic or epigenetic aberrations, suggesting...
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| Published in: | Oncotarget 2017-10, Vol.8 (49), p.86799-86815 |
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| Main Authors: | , , , , , , , |
| Format: | Article |
| Language: | English |
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| cites | cdi_FETCH-LOGICAL-c462t-d8e14500a8aafacf7c55a810685918e37efeed319d16d03b36b52468093a07963 |
| container_end_page | 86815 |
| container_issue | 49 |
| container_start_page | 86799 |
| container_title | Oncotarget |
| container_volume | 8 |
| creator | Kim, Jung-Lye Ha, Geun-Hyoung Campo, Loredana Denning, Mitchell F Patel, Tarun B Osipo, Clodia Lin, Shiaw-Yih Breuer, Eun-Kyoung |
| description | BRCA1 is an important player in the DNA damage response signaling, and its deficiency results in genomic instability. A complete loss or significantly reduced BRCA1 protein expression is often found in sporadic breast cancer cases despite the absence of genetic or epigenetic aberrations, suggesting the existence of other regulatory mechanisms controlling BRCA1 protein expression. Herein, we demonstrate that Fyn-related kinase (Frk)/Rak plays an important role in maintaining genomic stability, possibly in part through positively regulating BRCA1 protein stability and function via tyrosine phosphorylation on BRCA1 Tyr1552. In addition, Rak deficiency confers cellular sensitivity to DNA damaging agents and poly(ADP-ribose) polymerase (PARP) inhibitors. Overall, our findings highlight a critical role of Rak in the maintenance of genomic stability, at least in part, through protecting BRCA1 and provide novel treatment strategies for patients with breast tumors lacking Rak. |
| doi_str_mv | 10.18632/oncotarget.5717 |
| format | article |
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A complete loss or significantly reduced BRCA1 protein expression is often found in sporadic breast cancer cases despite the absence of genetic or epigenetic aberrations, suggesting the existence of other regulatory mechanisms controlling BRCA1 protein expression. Herein, we demonstrate that Fyn-related kinase (Frk)/Rak plays an important role in maintaining genomic stability, possibly in part through positively regulating BRCA1 protein stability and function via tyrosine phosphorylation on BRCA1 Tyr1552. In addition, Rak deficiency confers cellular sensitivity to DNA damaging agents and poly(ADP-ribose) polymerase (PARP) inhibitors. Overall, our findings highlight a critical role of Rak in the maintenance of genomic stability, at least in part, through protecting BRCA1 and provide novel treatment strategies for patients with breast tumors lacking Rak.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.5717</identifier><identifier>PMID: 29156836</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Research Paper</subject><ispartof>Oncotarget, 2017-10, Vol.8 (49), p.86799-86815</ispartof><rights>Copyright: © 2017 Kim et al. 2017</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c462t-d8e14500a8aafacf7c55a810685918e37efeed319d16d03b36b52468093a07963</citedby><cites>FETCH-LOGICAL-c462t-d8e14500a8aafacf7c55a810685918e37efeed319d16d03b36b52468093a07963</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689726/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689726/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,733,786,790,891,27957,27958,53827,53829</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29156836$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Jung-Lye</creatorcontrib><creatorcontrib>Ha, Geun-Hyoung</creatorcontrib><creatorcontrib>Campo, Loredana</creatorcontrib><creatorcontrib>Denning, Mitchell F</creatorcontrib><creatorcontrib>Patel, Tarun B</creatorcontrib><creatorcontrib>Osipo, Clodia</creatorcontrib><creatorcontrib>Lin, Shiaw-Yih</creatorcontrib><creatorcontrib>Breuer, Eun-Kyoung</creatorcontrib><title>The role of Rak in the regulation of stability and function of BRCA1</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>BRCA1 is an important player in the DNA damage response signaling, and its deficiency results in genomic instability. 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A complete loss or significantly reduced BRCA1 protein expression is often found in sporadic breast cancer cases despite the absence of genetic or epigenetic aberrations, suggesting the existence of other regulatory mechanisms controlling BRCA1 protein expression. Herein, we demonstrate that Fyn-related kinase (Frk)/Rak plays an important role in maintaining genomic stability, possibly in part through positively regulating BRCA1 protein stability and function via tyrosine phosphorylation on BRCA1 Tyr1552. In addition, Rak deficiency confers cellular sensitivity to DNA damaging agents and poly(ADP-ribose) polymerase (PARP) inhibitors. 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| language | eng |
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| source | PubMed Central |
| subjects | Research Paper |
| title | The role of Rak in the regulation of stability and function of BRCA1 |
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