Overexpression of Zinc‐Finger Protein 777 (ZNF777) Inhibits Proliferation at Low Cell Density Through Down‐Regulation of FAM129A
ABSTRACT Krüppel‐associated box‐containing zinc finger proteins (KRAB‐ZFPs) regulate a wide range of cellular processes. KRAB‐ZFPs have a KRAB domain, which binds to transcriptional corepressors, and a zinc finger domain, which binds to DNA to activate or repress gene transcription. Here, we charact...
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| Veröffentlicht in: | Journal of cellular biochemistry 2015-06, Vol.116 (6), p.954-968 |
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| creator | Yuki, Ryuzaburo Aoyama, Kazumasa Kubota, Sho Yamaguchi, Noritaka Kubota, Shoichi Hasegawa, Hitomi Morii, Mariko Huang, Xiayu Liu, Kang Williams, Roy Fukuda, Michiko N. Yamaguchi, Naoto |
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Krüppel‐associated box‐containing zinc finger proteins (KRAB‐ZFPs) regulate a wide range of cellular processes. KRAB‐ZFPs have a KRAB domain, which binds to transcriptional corepressors, and a zinc finger domain, which binds to DNA to activate or repress gene transcription. Here, we characterize ZNF777, a member of KRAB‐ZFPs. We show that ZNF777 localizes to the nucleus and inducible overexpression of ZNF777 inhibits cell proliferation in a manner dependent on its zinc finger domain but independent of its KRAB domain. Intriguingly, ZNF777 overexpression drastically inhibits cell proliferation at low cell density but slightly inhibits cell proliferation at high cell density. Furthermore, ZNF777 overexpression decreases the mRNA level of FAM129A irrespective of cell density. Importantly, the protein level of FAM129A strongly decreases at low cell density, but at high cell density the protein level of FAM129A does not decrease to that observed at low cell density. ZNF777‐mediated inhibition of cell proliferation is attenuated by overexpression of FAM129A at low cell density. Furthermore, ZNF777‐mediated down‐regulation of FAM129A induces moderate levels of the cyclin‐dependent kinase inhibitor p21. These results suggest that ZNF777 overexpression inhibits cell proliferation at low cell density and that p21 induction by ZNF777‐mediated down‐regulation of FAM129A plays a role in inhibition of cell proliferation. J. Cell. Biochem. 116: 954–968, 2015. © 2015 Wiley Periodicals, Inc. |
| doi_str_mv | 10.1002/jcb.25046 |
| format | Article |
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Krüppel‐associated box‐containing zinc finger proteins (KRAB‐ZFPs) regulate a wide range of cellular processes. KRAB‐ZFPs have a KRAB domain, which binds to transcriptional corepressors, and a zinc finger domain, which binds to DNA to activate or repress gene transcription. Here, we characterize ZNF777, a member of KRAB‐ZFPs. We show that ZNF777 localizes to the nucleus and inducible overexpression of ZNF777 inhibits cell proliferation in a manner dependent on its zinc finger domain but independent of its KRAB domain. Intriguingly, ZNF777 overexpression drastically inhibits cell proliferation at low cell density but slightly inhibits cell proliferation at high cell density. Furthermore, ZNF777 overexpression decreases the mRNA level of FAM129A irrespective of cell density. Importantly, the protein level of FAM129A strongly decreases at low cell density, but at high cell density the protein level of FAM129A does not decrease to that observed at low cell density. ZNF777‐mediated inhibition of cell proliferation is attenuated by overexpression of FAM129A at low cell density. Furthermore, ZNF777‐mediated down‐regulation of FAM129A induces moderate levels of the cyclin‐dependent kinase inhibitor p21. These results suggest that ZNF777 overexpression inhibits cell proliferation at low cell density and that p21 induction by ZNF777‐mediated down‐regulation of FAM129A plays a role in inhibition of cell proliferation. J. Cell. Biochem. 116: 954–968, 2015. © 2015 Wiley Periodicals, Inc.</description><identifier>ISSN: 0730-2312</identifier><identifier>EISSN: 1097-4644</identifier><identifier>DOI: 10.1002/jcb.25046</identifier><identifier>PMID: 25560148</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Biomarkers, Tumor - metabolism ; Blotting, Western ; CELL DENSITY ; Cell growth ; CELL PROLIFERATION ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Cyclin-dependent kinase inhibitor p21 ; Cyclin-Dependent Kinase Inhibitor p21 - genetics ; Cyclin-Dependent Kinase Inhibitor p21 - metabolism ; Density ; Deoxyribonucleic acid ; DNA ; Domains ; Enzyme inhibitors ; FAM129A ; Flow Cytometry ; HeLa Cells ; Humans ; Kinases ; Neoplasm Proteins - metabolism ; NIBAN ; p21 ; Proteins ; Repressor Proteins - genetics ; Repressor Proteins - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; RNA Interference ; Transcription ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Zinc ; Zinc finger proteins ; ZNF777</subject><ispartof>Journal of cellular biochemistry, 2015-06, Vol.116 (6), p.954-968</ispartof><rights>2015 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4476-e85f6318e28d6f10ef14d0281fb7efc3d7d8d8a459f89865c0c842084ca7e6b93</citedby><cites>FETCH-LOGICAL-c4476-e85f6318e28d6f10ef14d0281fb7efc3d7d8d8a459f89865c0c842084ca7e6b93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcb.25046$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcb.25046$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25560148$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yuki, Ryuzaburo</creatorcontrib><creatorcontrib>Aoyama, Kazumasa</creatorcontrib><creatorcontrib>Kubota, Sho</creatorcontrib><creatorcontrib>Yamaguchi, Noritaka</creatorcontrib><creatorcontrib>Kubota, Shoichi</creatorcontrib><creatorcontrib>Hasegawa, Hitomi</creatorcontrib><creatorcontrib>Morii, Mariko</creatorcontrib><creatorcontrib>Huang, Xiayu</creatorcontrib><creatorcontrib>Liu, Kang</creatorcontrib><creatorcontrib>Williams, Roy</creatorcontrib><creatorcontrib>Fukuda, Michiko N.</creatorcontrib><creatorcontrib>Yamaguchi, Naoto</creatorcontrib><title>Overexpression of Zinc‐Finger Protein 777 (ZNF777) Inhibits Proliferation at Low Cell Density Through Down‐Regulation of FAM129A</title><title>Journal of cellular biochemistry</title><addtitle>J Cell Biochem</addtitle><description>ABSTRACT
Krüppel‐associated box‐containing zinc finger proteins (KRAB‐ZFPs) regulate a wide range of cellular processes. KRAB‐ZFPs have a KRAB domain, which binds to transcriptional corepressors, and a zinc finger domain, which binds to DNA to activate or repress gene transcription. Here, we characterize ZNF777, a member of KRAB‐ZFPs. We show that ZNF777 localizes to the nucleus and inducible overexpression of ZNF777 inhibits cell proliferation in a manner dependent on its zinc finger domain but independent of its KRAB domain. Intriguingly, ZNF777 overexpression drastically inhibits cell proliferation at low cell density but slightly inhibits cell proliferation at high cell density. Furthermore, ZNF777 overexpression decreases the mRNA level of FAM129A irrespective of cell density. Importantly, the protein level of FAM129A strongly decreases at low cell density, but at high cell density the protein level of FAM129A does not decrease to that observed at low cell density. ZNF777‐mediated inhibition of cell proliferation is attenuated by overexpression of FAM129A at low cell density. Furthermore, ZNF777‐mediated down‐regulation of FAM129A induces moderate levels of the cyclin‐dependent kinase inhibitor p21. These results suggest that ZNF777 overexpression inhibits cell proliferation at low cell density and that p21 induction by ZNF777‐mediated down‐regulation of FAM129A plays a role in inhibition of cell proliferation. J. Cell. Biochem. 116: 954–968, 2015. © 2015 Wiley Periodicals, Inc.</description><subject>Biomarkers, Tumor - metabolism</subject><subject>Blotting, Western</subject><subject>CELL DENSITY</subject><subject>Cell growth</subject><subject>CELL PROLIFERATION</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Cyclin-dependent kinase inhibitor p21</subject><subject>Cyclin-Dependent Kinase Inhibitor p21 - genetics</subject><subject>Cyclin-Dependent Kinase Inhibitor p21 - metabolism</subject><subject>Density</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Domains</subject><subject>Enzyme inhibitors</subject><subject>FAM129A</subject><subject>Flow Cytometry</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Kinases</subject><subject>Neoplasm Proteins - metabolism</subject><subject>NIBAN</subject><subject>p21</subject><subject>Proteins</subject><subject>Repressor Proteins - genetics</subject><subject>Repressor Proteins - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA Interference</subject><subject>Transcription</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Zinc</subject><subject>Zinc finger proteins</subject><subject>ZNF777</subject><issn>0730-2312</issn><issn>1097-4644</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1uEzEQxy0EomnhwAsgS1zaw7b-Wtt7DCmBokARKpderP0YJ44262DvkubGgQfgGXkSHLZwQILTHOY3vxnNH6FnlJxTQtjFuq7OWU6EfIAmlBQqE1KIh2hCFCcZ45QdoeMY14SQouDsMTpieS4JFXqCvl1_gQB32wAxOt9hb_Gt6-ofX7_PXbeEgD8E34PrsFIKn96-n6d6hq-6latcHw_d1lkIZX8YLnu88Ds8g7bFl9BF1-_xzSr4YbnCl37XJetHWA7tSKdV8-k7yorpE_TIlm2Ep_f1BH2av7qZvckW16-vZtNFVguhZAY6t5JTDUw30lICloqGME1tpcDWvFGNbnQp8sLqQsu8JrUWjGhRlwpkVfATdDp6t8F_HiD2ZuNina4tO_BDNFSmhymhtEzoi7_QtR9Cl64zLP2OE56r4n9UcjFKFdc8UWcjVQcfYwBrtsFtyrA3lJhDgCYFaH4FmNjn98ah2kDzh_ydWAIuRmDnWtj_22Tezl6Oyp-3laNF</recordid><startdate>201506</startdate><enddate>201506</enddate><creator>Yuki, Ryuzaburo</creator><creator>Aoyama, Kazumasa</creator><creator>Kubota, Sho</creator><creator>Yamaguchi, Noritaka</creator><creator>Kubota, Shoichi</creator><creator>Hasegawa, Hitomi</creator><creator>Morii, Mariko</creator><creator>Huang, Xiayu</creator><creator>Liu, Kang</creator><creator>Williams, Roy</creator><creator>Fukuda, Michiko N.</creator><creator>Yamaguchi, Naoto</creator><general>Wiley Subscription Services, Inc</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>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T7</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201506</creationdate><title>Overexpression of Zinc‐Finger Protein 777 (ZNF777) Inhibits Proliferation at Low Cell Density Through Down‐Regulation of FAM129A</title><author>Yuki, Ryuzaburo ; Aoyama, Kazumasa ; Kubota, Sho ; Yamaguchi, Noritaka ; Kubota, Shoichi ; Hasegawa, Hitomi ; Morii, Mariko ; Huang, Xiayu ; Liu, Kang ; Williams, Roy ; Fukuda, Michiko N. ; Yamaguchi, Naoto</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4476-e85f6318e28d6f10ef14d0281fb7efc3d7d8d8a459f89865c0c842084ca7e6b93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Biomarkers, Tumor - metabolism</topic><topic>Blotting, Western</topic><topic>CELL DENSITY</topic><topic>Cell growth</topic><topic>CELL PROLIFERATION</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Cyclin-dependent kinase inhibitor p21</topic><topic>Cyclin-Dependent Kinase Inhibitor p21 - genetics</topic><topic>Cyclin-Dependent Kinase Inhibitor p21 - metabolism</topic><topic>Density</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Domains</topic><topic>Enzyme inhibitors</topic><topic>FAM129A</topic><topic>Flow Cytometry</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Kinases</topic><topic>Neoplasm Proteins - metabolism</topic><topic>NIBAN</topic><topic>p21</topic><topic>Proteins</topic><topic>Repressor Proteins - genetics</topic><topic>Repressor Proteins - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA Interference</topic><topic>Transcription</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Zinc</topic><topic>Zinc finger proteins</topic><topic>ZNF777</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yuki, Ryuzaburo</creatorcontrib><creatorcontrib>Aoyama, Kazumasa</creatorcontrib><creatorcontrib>Kubota, Sho</creatorcontrib><creatorcontrib>Yamaguchi, Noritaka</creatorcontrib><creatorcontrib>Kubota, Shoichi</creatorcontrib><creatorcontrib>Hasegawa, Hitomi</creatorcontrib><creatorcontrib>Morii, Mariko</creatorcontrib><creatorcontrib>Huang, Xiayu</creatorcontrib><creatorcontrib>Liu, Kang</creatorcontrib><creatorcontrib>Williams, Roy</creatorcontrib><creatorcontrib>Fukuda, Michiko N.</creatorcontrib><creatorcontrib>Yamaguchi, Naoto</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cellular biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yuki, Ryuzaburo</au><au>Aoyama, Kazumasa</au><au>Kubota, Sho</au><au>Yamaguchi, Noritaka</au><au>Kubota, Shoichi</au><au>Hasegawa, Hitomi</au><au>Morii, Mariko</au><au>Huang, Xiayu</au><au>Liu, Kang</au><au>Williams, Roy</au><au>Fukuda, Michiko N.</au><au>Yamaguchi, Naoto</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Overexpression of Zinc‐Finger Protein 777 (ZNF777) Inhibits Proliferation at Low Cell Density Through Down‐Regulation of FAM129A</atitle><jtitle>Journal of cellular biochemistry</jtitle><addtitle>J Cell Biochem</addtitle><date>2015-06</date><risdate>2015</risdate><volume>116</volume><issue>6</issue><spage>954</spage><epage>968</epage><pages>954-968</pages><issn>0730-2312</issn><eissn>1097-4644</eissn><abstract>ABSTRACT
Krüppel‐associated box‐containing zinc finger proteins (KRAB‐ZFPs) regulate a wide range of cellular processes. KRAB‐ZFPs have a KRAB domain, which binds to transcriptional corepressors, and a zinc finger domain, which binds to DNA to activate or repress gene transcription. Here, we characterize ZNF777, a member of KRAB‐ZFPs. We show that ZNF777 localizes to the nucleus and inducible overexpression of ZNF777 inhibits cell proliferation in a manner dependent on its zinc finger domain but independent of its KRAB domain. Intriguingly, ZNF777 overexpression drastically inhibits cell proliferation at low cell density but slightly inhibits cell proliferation at high cell density. Furthermore, ZNF777 overexpression decreases the mRNA level of FAM129A irrespective of cell density. Importantly, the protein level of FAM129A strongly decreases at low cell density, but at high cell density the protein level of FAM129A does not decrease to that observed at low cell density. ZNF777‐mediated inhibition of cell proliferation is attenuated by overexpression of FAM129A at low cell density. Furthermore, ZNF777‐mediated down‐regulation of FAM129A induces moderate levels of the cyclin‐dependent kinase inhibitor p21. These results suggest that ZNF777 overexpression inhibits cell proliferation at low cell density and that p21 induction by ZNF777‐mediated down‐regulation of FAM129A plays a role in inhibition of cell proliferation. J. Cell. Biochem. 116: 954–968, 2015. © 2015 Wiley Periodicals, Inc.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>25560148</pmid><doi>10.1002/jcb.25046</doi><tpages>15</tpages></addata></record> |
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| subjects | Biomarkers, Tumor - metabolism Blotting, Western CELL DENSITY Cell growth CELL PROLIFERATION Cell Proliferation - drug effects Cell Survival - drug effects Cyclin-dependent kinase inhibitor p21 Cyclin-Dependent Kinase Inhibitor p21 - genetics Cyclin-Dependent Kinase Inhibitor p21 - metabolism Density Deoxyribonucleic acid DNA Domains Enzyme inhibitors FAM129A Flow Cytometry HeLa Cells Humans Kinases Neoplasm Proteins - metabolism NIBAN p21 Proteins Repressor Proteins - genetics Repressor Proteins - metabolism Reverse Transcriptase Polymerase Chain Reaction RNA Interference Transcription Transcription Factors - genetics Transcription Factors - metabolism Zinc Zinc finger proteins ZNF777 |
| title | Overexpression of Zinc‐Finger Protein 777 (ZNF777) Inhibits Proliferation at Low Cell Density Through Down‐Regulation of FAM129A |
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