title: 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 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.
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 260-8675, Japan.
authors.forename: Ryuzaburo
authors.initials: R
authors.lastname: Yuki
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Aoyama
authors.forename: Sho
authors.initials: S
authors.lastname: Kubota
authors.forename: Noritaka
authors.initials: N
authors.lastname: Yamaguchi
authors.forename: Shoichi
authors.initials: S
authors.lastname: Kubota
authors.forename: Hitomi
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Mariko
authors.initials: M
authors.lastname: Morii
authors.forename: Xiayu
authors.initials: X
authors.lastname: Huang
authors.forename: Kang
authors.initials: K
authors.lastname: Liu
authors.forename: Roy
authors.initials: R
authors.lastname: Williams
authors.forename: Michiko N
authors.initials: MN
authors.lastname: Fukuda
authors.forename: Naoto
authors.initials: N
authors.lastname: Yamaguchi
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins
chemical_list: D014408:Biomarkers, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C516108:NIBAN1 protein, human; D051017:Apoptosis Regulatory Proteins
keywords: CELL DENSITY; CELL PROLIFERATION; FAM129A; NIBAN; ZNF777; p21