Overexpression of CR/periphilin downregulates Cdc7 expression and induces S-phase arrest.
Cdc7 expression repressor (CR)/periphilin has been originally cloned as an interactor with periplakin, a precursor of the cornified cell envelope, and suggested to constitute a new type of nuclear matrix. We here show that CR/periphilin is a ubiquitously expressed nuclear protein with speckled distribution. Overexpression of CR/periphilin induces S-phase arrest. Analysis of expression of regulators involved in DNA replication has revealed that both mRNA and protein expression of Cdc7, a regulator of the initiation and continuation of DNA replication, are markedly downregulated by overexpression of CR/periphilin. However, co-expression of Cdc7 only marginally rescues S-phase arrest induced by CR, indicating that CR retards S-phase progression by modifying expression of some genes including Cdc7, which are involved in progression of DNA replication or coordination of DNA replication and S-phase progression.
Department of Pharmacology, KEIO University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Megumi
M
Kurita
Hiroaki
H
Suzuki
Hisao
H
Masai
Kiyohisa
K
Mizumoto
Etsuro
E
Ogata
Ikuo
I
Nishimoto
Sadakazu
S
Aiso
Masaaki
M
Matsuoka
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000951:Antigens, Neoplasm; D015152:Blotting, Northern; D019556:COS Cells; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D020224:Expressed Sequence Tags; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D015603:Keratinocytes / Q000378:metabolism; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000096:biosynthesis*; D010957:Plasmids / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D016196:S Phase
D000951:Antigens, Neoplasm; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D009687:Nuclear Proteins; C478775:PPHLN1 protein, human; D020033:Protein Isoforms; D012333:RNA, Messenger; D004247:DNA; C068619:CDC7 protein, human; D017346:Protein Serine-Threonine Kinases