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CC BY V4.0, Open Access
CC BY V4.0, Open Access
Journal article
KPNB1 mediates PER/CRY nuclear translocation and circadian clock function
eLife, Vol.4(2015), e08647
08/29/2015
PMID: 26319354
Abstract
Regulated nuclear translocation of the PER/CRY repressor complex is critical for negative feedback regulation of the circadian clock of mammals. However, the precise molecular mechanism is not fully understood. Here, we report that KPNB1, an importin β component of the ncRNA repressor of nuclear factor of activated T cells (NRON) ribonucleoprotein complex, mediates nuclear translocation and repressor function of the PER/CRY complex. RNAi depletion of KPNB1 traps the PER/CRY complex in the cytoplasm by blocking nuclear entry of PER proteins in human cells. KPNB1 interacts mainly with PER proteins and directs PER/CRY nuclear transport in a circadian fashion. Interestingly, KPNB1 regulates the PER/CRY nuclear entry and repressor function, independently of importin α, its classical partner. Moreover, inducible inhibition of the conserved Drosophila importin β in lateral neurons abolishes behavioral rhythms in flies. Collectively, these data show that KPNB1 is required for timely nuclear import of PER/CRY in the negative feedback regulation of the circadian clock.
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Details
- Title
- KPNB1 mediates PER/CRY nuclear translocation and circadian clock function
- Creators
- Yool Lee - Washington State University, Biomedical Sciences, Department ofA Reum Jang - Howard Hughes Medical InstituteLauren J Francey - Cincinnati Children's Hospital Medical CenterAmita Sehgal - University of PennsylvaniaJohn B Hogenesch - Cincinnati Children's Hospital Medical Center
- Publication Details
- eLife, Vol.4(2015), e08647
- Academic Unit
- Elson S. Floyd College of Medicine
- Grant note
- P30 ES013508 / NIEHS NIH HHS T32 ES019851 / NIEHS NIH HHS R01 NS054794 / NINDS NIH HHS R01 NS048471 / NINDS NIH HHS 1R01NS054794-06 / NINDS NIH HHS R37 NS048471 / NINDS NIH HHS
- Identifiers
- 99901132535301842
- Language
- English
- Resource Type
- Journal article