13 research outputs found
Dimerization and nuclear entry of mPER proteins in mammalian cells
Nuclear entry of circadian oscillatory gene products is a key step for the
generation of a 24-hr cycle of the biological clock. We have examined
nuclear import of clock proteins of the mammalian period gene family and
the effect of serum shock, which induces a synchronous clock in cultured
cells. Previously, mCRY1 and mCRY2 have been found to complex with PER
proteins leading to nuclear import. Here we report that nuclear
translocation of mPER1 and mPER2 (1) involves physical interactions with
mPER3, (2) is accelerated by serum treatment, and (3) still occurs in
mCry1/mCry2 double-deficient cells lacking a functional biological clock.
Moreover, nuclear localization of endogenous mPER1 was observed in
cultured mCry1/mCry2 double-deficient cells as well as in the liver and
the suprachiasmatic nuclei (SCN) of mCry1/mCry2 double-mutant mice. This
indicates that nuclear translocation of at least mPER1 also can occur
under physiological conditions (i.e., in the intact mouse) in the absence
of any CRY protein. The mPER3 amino acid sequence predicts the presence of
a cytoplasmic localization domain (CLD) and a nuclear localization signal
(NLS). Deletion analysis suggests that the interplay of the CLD and NLS
proposed to regulate nuclear entry of PER in Drosophila is conserved in
mammals, but with the novel twist that mPER3 can act as the dimerizing
partner