PDZRN3 protects against apoptosis in myoblasts by maintaining cyclin A2 expression
PDZRN3 is a PDZ domain-containing RING-finger family protein that functions in various developmental processes. We previously showed that expression of PDZRN3 is induced together with that of MyoD during the early phase of skeletal muscle regeneration in vivo . We here show that PDZRN3 suppresses ap...
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| description | PDZRN3 is a PDZ domain-containing RING-finger family protein that functions in various developmental processes. We previously showed that expression of PDZRN3 is induced together with that of MyoD during the early phase of skeletal muscle regeneration
in vivo
. We here show that PDZRN3 suppresses apoptosis and promotes proliferation in myoblasts in a manner dependent on cyclin A2. Depletion of PDZRN3 in mouse C2C12 myoblasts by RNA interference reduced the proportion of Ki-67-positive cells and the level of Akt phosphorylation, implicating PDZRN3 in regulation of both cell proliferation and apoptosis. Exposure of C2C12 cells as well as of C3H10T1/2 mesenchymal stem cells and NIH-3T3 fibroblasts to various inducers of apoptosis including serum deprivation resulted in a greater increase in the amount of cleaved caspase-3 in PDZRN3-depleted cells than in control cells. The abundance of cyclin A2 was reduced in PDZRN3-depleted C2C12 myoblasts, as was that of Mre11, which contributes to the repair of DNA damage. Overexpression of cyclin A2 restored the expression of Mre11 and Ki-67 as well as attenuated caspase-3 cleavage in PDZRN3-depleted cells deprived of serum. These results indicate that PDZRN3 suppresses apoptosis and promotes proliferation in myoblasts and other cell types by maintaining cyclin A2 expression. |
| doi_str_mv | 10.1038/s41598-020-58116-1 |
| format | Article |
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in vivo
. We here show that PDZRN3 suppresses apoptosis and promotes proliferation in myoblasts in a manner dependent on cyclin A2. Depletion of PDZRN3 in mouse C2C12 myoblasts by RNA interference reduced the proportion of Ki-67-positive cells and the level of Akt phosphorylation, implicating PDZRN3 in regulation of both cell proliferation and apoptosis. Exposure of C2C12 cells as well as of C3H10T1/2 mesenchymal stem cells and NIH-3T3 fibroblasts to various inducers of apoptosis including serum deprivation resulted in a greater increase in the amount of cleaved caspase-3 in PDZRN3-depleted cells than in control cells. The abundance of cyclin A2 was reduced in PDZRN3-depleted C2C12 myoblasts, as was that of Mre11, which contributes to the repair of DNA damage. Overexpression of cyclin A2 restored the expression of Mre11 and Ki-67 as well as attenuated caspase-3 cleavage in PDZRN3-depleted cells deprived of serum. These results indicate that PDZRN3 suppresses apoptosis and promotes proliferation in myoblasts and other cell types by maintaining cyclin A2 expression.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-58116-1</identifier><identifier>PMID: 31980707</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/2 ; 13/89 ; 13/95 ; 631/337/641 ; 631/80/82/23 ; AKT protein ; Animals ; Apoptosis ; Apoptosis - physiology ; Caspase-3 ; Cell Adhesion ; Cell Cycle ; Cell Division ; Cell proliferation ; Cells, Cultured ; Cyclin A2 - biosynthesis ; Cyclin A2 - genetics ; DNA Damage ; DNA repair ; Down-Regulation ; Fibroblasts ; Gene Expression Regulation ; Genomic Instability ; Humanities and Social Sciences ; Mesenchymal Stem Cells - metabolism ; Mesenchyme ; Mice ; MRE11 protein ; multidisciplinary ; Myoblasts ; Myoblasts - cytology ; Myoblasts - metabolism ; MyoD protein ; Phosphorylation ; RNA Interference ; RNA, Messenger - biosynthesis ; RNA, Messenger - genetics ; RNA, Small Interfering - genetics ; RNA, Small Interfering - pharmacology ; RNA-mediated interference ; Science ; Science (multidisciplinary) ; Skeletal muscle ; Stem cell transplantation ; Stem cells ; Ubiquitin-Protein Ligases - physiology</subject><ispartof>Scientific reports, 2020-01, Vol.10 (1), p.1140-1140, Article 1140</ispartof><rights>The Author(s) 2020</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c577t-48a201bb4d770c5eee24bde1899b9eedcb62443c21efa9e71a1407ac6270ee1c3</citedby><cites>FETCH-LOGICAL-c577t-48a201bb4d770c5eee24bde1899b9eedcb62443c21efa9e71a1407ac6270ee1c3</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/PMC6981127/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981127/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31980707$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Honda, Takeshi</creatorcontrib><creatorcontrib>Inui, Makoto</creatorcontrib><title>PDZRN3 protects against apoptosis in myoblasts by maintaining cyclin A2 expression</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>PDZRN3 is a PDZ domain-containing RING-finger family protein that functions in various developmental processes. We previously showed that expression of PDZRN3 is induced together with that of MyoD during the early phase of skeletal muscle regeneration
in vivo
. We here show that PDZRN3 suppresses apoptosis and promotes proliferation in myoblasts in a manner dependent on cyclin A2. Depletion of PDZRN3 in mouse C2C12 myoblasts by RNA interference reduced the proportion of Ki-67-positive cells and the level of Akt phosphorylation, implicating PDZRN3 in regulation of both cell proliferation and apoptosis. Exposure of C2C12 cells as well as of C3H10T1/2 mesenchymal stem cells and NIH-3T3 fibroblasts to various inducers of apoptosis including serum deprivation resulted in a greater increase in the amount of cleaved caspase-3 in PDZRN3-depleted cells than in control cells. The abundance of cyclin A2 was reduced in PDZRN3-depleted C2C12 myoblasts, as was that of Mre11, which contributes to the repair of DNA damage. Overexpression of cyclin A2 restored the expression of Mre11 and Ki-67 as well as attenuated caspase-3 cleavage in PDZRN3-depleted cells deprived of serum. These results indicate that PDZRN3 suppresses apoptosis and promotes proliferation in myoblasts and other cell types by maintaining cyclin A2 expression.</description><subject>13/2</subject><subject>13/89</subject><subject>13/95</subject><subject>631/337/641</subject><subject>631/80/82/23</subject><subject>AKT protein</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - physiology</subject><subject>Caspase-3</subject><subject>Cell Adhesion</subject><subject>Cell Cycle</subject><subject>Cell Division</subject><subject>Cell proliferation</subject><subject>Cells, Cultured</subject><subject>Cyclin A2 - biosynthesis</subject><subject>Cyclin A2 - genetics</subject><subject>DNA Damage</subject><subject>DNA repair</subject><subject>Down-Regulation</subject><subject>Fibroblasts</subject><subject>Gene Expression Regulation</subject><subject>Genomic Instability</subject><subject>Humanities and Social Sciences</subject><subject>Mesenchymal Stem Cells - metabolism</subject><subject>Mesenchyme</subject><subject>Mice</subject><subject>MRE11 protein</subject><subject>multidisciplinary</subject><subject>Myoblasts</subject><subject>Myoblasts - cytology</subject><subject>Myoblasts - metabolism</subject><subject>MyoD protein</subject><subject>Phosphorylation</subject><subject>RNA Interference</subject><subject>RNA, Messenger - biosynthesis</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Small Interfering - genetics</subject><subject>RNA, Small Interfering - pharmacology</subject><subject>RNA-mediated interference</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Skeletal muscle</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Ubiquitin-Protein Ligases - physiology</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kUtr3DAUhUVo6YRJ_kAXwZBNN04lWbKsTSHk0RRCGkK66UbImjtTBVtydD0h8--r6SSTx6ICIcH57tG9OoR8ZvSI0ar5ioJJ3ZSU01I2jNUl2yG7nApZ8orzD6_uE7KPeEfzklwLpj-RScV0QxVVu-Tm-vT3zVVVDCmO4EYs7ML6gGNhhziMET0WPhT9KradxSy3q6LPwJi3D4vCrVyX9WNewOOQANHHsEc-zm2HsP90Tsmv87Pbk4vy8uf3HyfHl6WTSo2laCynrG3FTCnqJABw0c6ANVq3GmDm2poLUTnOYG41KGaZoMq6misKwFw1Jd82vsOy7TMPYUy2M0PyvU0rE603b5Xg_5hFfDC1zh_GVTb48mSQ4v0ScDS9RwddZwPEJRpeCSmp0FRm9PAdeheXKeTx1pSQQtS51ynhG8qliJhgvm2GUbNOzWxSMzk18y81w3LRwesxtiXPGWWg2gCYpbCA9PL2f2z_ArY9o3w</recordid><startdate>20200124</startdate><enddate>20200124</enddate><creator>Honda, Takeshi</creator><creator>Inui, Makoto</creator><general>Nature Publishing Group UK</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>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</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>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200124</creationdate><title>PDZRN3 protects against apoptosis in myoblasts by maintaining cyclin A2 expression</title><author>Honda, Takeshi ; Inui, Makoto</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c577t-48a201bb4d770c5eee24bde1899b9eedcb62443c21efa9e71a1407ac6270ee1c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>13/2</topic><topic>13/89</topic><topic>13/95</topic><topic>631/337/641</topic><topic>631/80/82/23</topic><topic>AKT protein</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - physiology</topic><topic>Caspase-3</topic><topic>Cell Adhesion</topic><topic>Cell Cycle</topic><topic>Cell Division</topic><topic>Cell proliferation</topic><topic>Cells, Cultured</topic><topic>Cyclin A2 - biosynthesis</topic><topic>Cyclin A2 - genetics</topic><topic>DNA Damage</topic><topic>DNA repair</topic><topic>Down-Regulation</topic><topic>Fibroblasts</topic><topic>Gene Expression Regulation</topic><topic>Genomic Instability</topic><topic>Humanities and Social Sciences</topic><topic>Mesenchymal Stem Cells - metabolism</topic><topic>Mesenchyme</topic><topic>Mice</topic><topic>MRE11 protein</topic><topic>multidisciplinary</topic><topic>Myoblasts</topic><topic>Myoblasts - cytology</topic><topic>Myoblasts - metabolism</topic><topic>MyoD protein</topic><topic>Phosphorylation</topic><topic>RNA Interference</topic><topic>RNA, Messenger - biosynthesis</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Small Interfering - genetics</topic><topic>RNA, Small Interfering - pharmacology</topic><topic>RNA-mediated interference</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Skeletal muscle</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Ubiquitin-Protein Ligases - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Honda, Takeshi</au><au>Inui, Makoto</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PDZRN3 protects against apoptosis in myoblasts by maintaining cyclin A2 expression</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-01-24</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>1140</spage><epage>1140</epage><pages>1140-1140</pages><artnum>1140</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>PDZRN3 is a PDZ domain-containing RING-finger family protein that functions in various developmental processes. We previously showed that expression of PDZRN3 is induced together with that of MyoD during the early phase of skeletal muscle regeneration
in vivo
. We here show that PDZRN3 suppresses apoptosis and promotes proliferation in myoblasts in a manner dependent on cyclin A2. Depletion of PDZRN3 in mouse C2C12 myoblasts by RNA interference reduced the proportion of Ki-67-positive cells and the level of Akt phosphorylation, implicating PDZRN3 in regulation of both cell proliferation and apoptosis. Exposure of C2C12 cells as well as of C3H10T1/2 mesenchymal stem cells and NIH-3T3 fibroblasts to various inducers of apoptosis including serum deprivation resulted in a greater increase in the amount of cleaved caspase-3 in PDZRN3-depleted cells than in control cells. The abundance of cyclin A2 was reduced in PDZRN3-depleted C2C12 myoblasts, as was that of Mre11, which contributes to the repair of DNA damage. Overexpression of cyclin A2 restored the expression of Mre11 and Ki-67 as well as attenuated caspase-3 cleavage in PDZRN3-depleted cells deprived of serum. These results indicate that PDZRN3 suppresses apoptosis and promotes proliferation in myoblasts and other cell types by maintaining cyclin A2 expression.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31980707</pmid><doi>10.1038/s41598-020-58116-1</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 13/2 13/89 13/95 631/337/641 631/80/82/23 AKT protein Animals Apoptosis Apoptosis - physiology Caspase-3 Cell Adhesion Cell Cycle Cell Division Cell proliferation Cells, Cultured Cyclin A2 - biosynthesis Cyclin A2 - genetics DNA Damage DNA repair Down-Regulation Fibroblasts Gene Expression Regulation Genomic Instability Humanities and Social Sciences Mesenchymal Stem Cells - metabolism Mesenchyme Mice MRE11 protein multidisciplinary Myoblasts Myoblasts - cytology Myoblasts - metabolism MyoD protein Phosphorylation RNA Interference RNA, Messenger - biosynthesis RNA, Messenger - genetics RNA, Small Interfering - genetics RNA, Small Interfering - pharmacology RNA-mediated interference Science Science (multidisciplinary) Skeletal muscle Stem cell transplantation Stem cells Ubiquitin-Protein Ligases - physiology |
| title | PDZRN3 protects against apoptosis in myoblasts by maintaining cyclin A2 expression |
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