Role for Slimb in the degradation of Drosophila Period protein phosphorylated by Doubletime

Hyuk Wan Ko, Jin Jiang, Isaac Edery

Research output: Contribution to journalArticle

237 Citations (Scopus)

Abstract

Protein phosphorylation has a key role in modulating the stabilities of circadian clock proteins in a manner specific to the time of day. A conserved feature of animal clocks is that Period (Per) proteins undergo daily rhythms in phosphorylation and levels, events that are crucial for normal clock progression. Casein kinase Iε (CKIε) has a prominent role in regulating the phosphorylation and abundance of Per proteins in animals. This was first shown in Drosophila with the characterization of Doubletime (Dbt), a homologue of vertebrate casein kinase Iε. However, it is not clear how Dbt regulates the levels of Per. Here we show, using a cell culture system, that Dbt promotes the progressive phosphorylation of Per, leading to the rapid degradation of hyperphosphorylated isoforms by the ubiquitin-proteasome pathway. Slimb, an F-box/WD40-repeat protein functioning in the ubiquitin-proteasome pathway interacts preferentially with phosphorylated Per and stimulates its degradation. Overexpression of slimb or expression in clock cells of a dominant-negative version of slimb disrupts normal rhythmic activity in flies. Our findings suggest that hyperphosphorylated Per is targeted to the proteasome by interactions with Slimb.

Original languageEnglish
Pages (from-to)673-678
Number of pages6
JournalNature
Volume420
Issue number6916
DOIs
Publication statusPublished - 2002 Dec 12

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Proteasome Endopeptidase Complex
Casein Kinase I
Period Circadian Proteins
Phosphorylation
Ubiquitin
Circadian Clocks
Proteins
Diptera
Drosophila
Vertebrates
Protein Isoforms
Cell Culture Techniques
Drosophila PER protein

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • General

Cite this

Ko, Hyuk Wan ; Jiang, Jin ; Edery, Isaac. / Role for Slimb in the degradation of Drosophila Period protein phosphorylated by Doubletime. In: Nature. 2002 ; Vol. 420, No. 6916. pp. 673-678.
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Role for Slimb in the degradation of Drosophila Period protein phosphorylated by Doubletime. / Ko, Hyuk Wan; Jiang, Jin; Edery, Isaac.

In: Nature, Vol. 420, No. 6916, 12.12.2002, p. 673-678.

Research output: Contribution to journalArticle

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