Dynamic interaction of p220(NPAT) and CBP/p300 promotes S-phase entry.
Cajal bodies contain cyclin E/cdk2 and the substrate p220(NPAT) to regulate the transcription of histones, which is essential for cell proliferation, however, recent mouse knockout studies indicate that cyclin E and cdk2 are dispensable for these events. Because the CBP/p300 histone acetyltransferase are also known to be involved in cell proliferation, we examined the molecular and functional interactions of p220(NPAT) with the CBP/p300 at the G1/S boundary as cell cycle regulators. The subnuclear localization of p220(NPAT) and CBP/p300 proteins showed that their foci partially overlapped in a cell cycle dependent manner. Overexpression of p220(NPAT) and CBP/p300 cooperatively enhanced G1/S transition and DNA synthesis even without cdk2 phosphorylation site. Finally, molecular alignment analysis indicated that p220(NPAT) contains several potential substrate sites for CBP/p300. Overall, our findings demonstrate that p220(NPAT) and CBP/p300 form a transient complex at the G1/S boundary to play cooperative roles to promote the S-phase entry.
Wang
Aiyan
A
Section of Molecular Craniofacial Embryology, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8549, Japan.
Ikura
Tsuyoshi
T
Eto
Kazuhiro
K
Ota
Masato S
MS
D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020541:Coiled Bodies / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis*; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology*; D016196:S Phase / Q000502:physiology*; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*
D018797:Cell Cycle Proteins; C101693:NPAT protein, human; D009687:Nuclear Proteins; D015534:Trans-Activators; D004247:DNA