tailieunhanh - Báo cáo khoa học: Nuclear import of mPER3 in Xenopus oocytes and HeLa cells requires complex formation with mPER1

Several transcription factors with the function of setting the biological clock in vertebrates have been described. A detailed understanding of their nucleocytolasmic transport properties may uncover novel aspects of the regulation of the circadian rhythm. This assumption led us to perform a systematic analysis of the nuclear import characteristics of the different murine PER and CRY proteins, usingXenopusoocytes and HeLa cells as experimental systems. | iFEBS Journal Nuclear import of mPER3 in Xenopus oocytes and HeLa cells requires complex formation with mPER1 Susanne Loop and Tomas Pieler Abteilung Entwicklungsbiochemie Zentrum fur Biochemie und Molekulare Zellbiologie Georg-August Universitat Gottingen Germany Keywords circadian rhythm mCRY mPER nuclear import Xenopus oocytes Several transcription factors with the function of setting the biological clock in vertebrates have been described. A detailed understanding of their nucleocytolasmic transport properties may uncover novel aspects of the Correspondence T. Pieler Abteilung Entwicklungsbiochemie Zentrum fur Biochemie und Molekulare Zellbiologie Georg-August Universitat Justus von Liebig Weg 11 D-37077 Gottingen Germany Fax 49 551 3914614 Tel 49 551 395683 E-mail tpieler@ regulation of the circadian rhythm. This assumption led us to perform a systematic analysis of the nuclear import characteristics of the different murine PER and CRY proteins using Xenopus oocytes and HeLa cells as experimental systems. Our major finding is that nuclear import of mPER3 requires complex formation with mPER1. We further show that the nuclear localization signal NLS function of mPER1 and not activation of a masked NLS in mPER3 is critical for the import of the mPER1-mPER3 complex. Finally and as previously described in other cell systems nuclear import of mPER proteins in Xenopus oocytes correlates positively with Received 14 March 2005 revised 27 May 2005 accepted 31 May 2005 their phosphorylation. doi The genetic control of circadian rhythmicity was first analysed in Drosophila. A central autoregulatory feedback loop that involves different transcriptional regulators was uncovered. The bHLH transcription factors CLOCK CLK and CYCLE CYC drive expression of the period per and timeless tim genes. Conversely Period and Timeless proteins PER and TIM inhibit CLK CYC-mediated transcription of their own genes resulting in a gradual loss of PER

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