FWD1-mediated degradation of FREQUENCY in Neurospora establishes a conserved mechanism for circadian clock regulation

Qun He, Ping Cheng, Yuhong Yang, Qiyang He, Hongtao Yu, Yi Liu

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4421-4430
Number of pages10
JournalEMBO Journal
Volume22
Issue number17
DOIs
StatePublished - Sep 1 2003

Fingerprint

Neurospora
Circadian Clocks
Circadian Rhythm
Clocks
SKP Cullin F-Box Protein Ligases
Period Circadian Proteins
Degradation
Ubiquitination
Diptera
Drosophila
Proteins
Phosphorylation
Gene Expression
Gene expression
Substrates
WD40 Repeats

Keywords

  • Circadian clock
  • FREQUENCY
  • FWD1
  • Neurospora
  • Proteasome

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

FWD1-mediated degradation of FREQUENCY in Neurospora establishes a conserved mechanism for circadian clock regulation. / He, Qun; Cheng, Ping; Yang, Yuhong; He, Qiyang; Yu, Hongtao; Liu, Yi.

In: EMBO Journal, Vol. 22, No. 17, 01.09.2003, p. 4421-4430.

Research output: Contribution to journalArticle

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