Overexpression of CR/periphilin downregulates Cdc7 expression and induces S-phase arrest |
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Authors: | Kurita Megumi Suzuki Hiroaki Masai Hisao Mizumoto Kiyohisa Ogata Etsuro Nishimoto Ikuo Aiso Sadakazu Matsuoka Masaaki |
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Affiliation: | Department of Pharmacology, KEIO University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. |
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Abstract: | 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. |
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Keywords: | CR Cdc7 S-phase arrest Cell cycle Periphilin |
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