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FWD1‐mediated degradation of FREQUENCY in Neurospora establishes a conserved mechanism for circadian clock regulation
Author(s) -
He Qun,
Cheng Ping,
Yang Yuhong,
He Qiyang,
Yu Hongtao,
Liu Yi
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg425
Subject(s) - biology , neurospora , circadian clock , mechanism (biology) , circadian rhythm , bacterial circadian rhythms , degradation (telecommunications) , microbiology and biotechnology , neurospora crassa , genetics , evolutionary biology , neuroscience , mutant , gene , telecommunications , philosophy , epistemology , computer science
Phosphorylation of the Neurospora circadian clock protein FREQUENCY (FRQ) regulates its degradation and the proper function of the clock. The mechanism by which FRQ undergoes degradation has not been established. Here we show that FRQ is likely ubiquitylated in vivo , and its proper degradation requires FWD1, an F‐box/WD‐40 repeat‐containing protein. In the fwd1 disruption strains, FRQ degradation is severely impaired, resulting in the accumulation of hyperphosphorylated FRQ. Furthermore, the circadian rhythms of gene expression and the circadian conidiation rhythms are abolished in these fwd1 mutants. Finally, FRQ and FWD1 interact physically in vivo , suggesting that FWD1 is the substrate‐recruiting subunit of an SCF‐type ubiquitin ligase responsible for FRQ ubiquitylation and degradation. Together with the recent finding that Slimb (the Drosophila homolog of FWD1) is involved in the degradation of the Period protein in flies, our results indicate that FWD1 regulates the degradation of FRQ in Neurospora and is an evolutionarily conserved component of the eukaryotic circadian clock.