Casein kinase II phosphorylates the fragile X mental retardation protein and modulates its biological properties

Mikiko C. Siomi, Kyoko Higashijima, Akira Ishizuka, Haruhiko Siomi

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Fragile X syndrome is caused by loss of FMR1 protein expression. FMR1 binds RNA and associates with polysomes in the cytoplasm; thus, it has been proposed to function as a regulator of gene expression at the posttranscriptional level. Posttranslational modification of FMR1 had previously been suggested to regulate its activity, but no experimental support for this model has been reported to date. Here we report that FMR1 in Drosophila melanogaster (dFMR1) is phosphorylated in vivo and that the homomer formation and the RNA-binding activities of dFMR1 are modulated by phosphorylation in vitro. Identification of a protein phosphorylating dFMR1 showed it to be Drosophila casein kinase II (dCKII). dCKII directly interacts with and phosphorylates dFMR1 in vitro. The phosphorylation site in dFMR1 was identified as Ser406, which is highly conserved among FMR1 family members from several species. Using mass spectrometry, we established that Ser406 of dFMR1 is indeed phosphorylated in vivo. Furthermore, human FMR1 (hFMR1) is also phosphorylated in vivo, and alteration of the conserved Ser500 in hFMR1 abolishes phosphorylation by CKII in vitro. These studies support the model that the biological functions of FMR1, such as regulation of gene expression, are likely regulated by its phosphorylation.

Original languageEnglish
Pages (from-to)8438-8447
Number of pages10
JournalMolecular and Cellular Biology
Volume22
Issue number24
DOIs
Publication statusPublished - 2002 Dec
Externally publishedYes

Fingerprint

Fragile X Mental Retardation Protein
Casein Kinase II
Phosphorylation
Drosophila
RNA
Fragile X Syndrome
Biological Models
Polyribosomes
Gene Expression Regulation
Post Translational Protein Processing
Regulator Genes
Drosophila melanogaster
Mass Spectrometry
Cytoplasm
Proteins
Theoretical Models
Gene Expression
In Vitro Techniques

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Casein kinase II phosphorylates the fragile X mental retardation protein and modulates its biological properties. / Siomi, Mikiko C.; Higashijima, Kyoko; Ishizuka, Akira; Siomi, Haruhiko.

In: Molecular and Cellular Biology, Vol. 22, No. 24, 12.2002, p. 8438-8447.

Research output: Contribution to journalArticle

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