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, 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 their phosphorylation.