Inhibition of MuSK expression by CREB interacting with a CRE-like element and MyoD

Chang Hoon Kim, Wencheng Xiong, Lin Mei

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The type I receptor-like protein tyrosine kinase MuSK is essential for the neuromuscular junction formation. MuSK expression is tightly regulated during development, but the underlying mechanisms were unclear. Here we identified a novel mechanism by which MuSK expression may be regulated. A cyclic AMP response element (CRE)-like element in the 5′-flanking region of the MuSK gene binds to CREB1 (CRE-binding protein 1). Mutation of this element increases the MuSK promoter activity, suggesting a role for CREB1 in attenuation of MuSK expression. Interestingly, CREB mutants unable to bind to DNA also inhibit MuSK promoter activity, suggesting a CRE-independent inhibitory mechanism. In agreement, CREB1 could inhibit a mutant MuSK transgene reporter whose CRE site was mutated. We provide evidence that CREB interacts directly with MyoD, a myogenic factor essential for MuSK expression in muscle cells. Suppression of CREB expression by small interfering RNA increases MuSK promoter activity. These results demonstrate an important role for CREB1 in the regulation of MuSK expression.

Original languageEnglish (US)
Pages (from-to)5329-5338
Number of pages10
JournalMolecular and Cellular Biology
Volume25
Issue number13
DOIs
StatePublished - Jul 1 2005

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Activating Transcription Factor 2
Response Elements
Cyclic AMP
Cyclic AMP Response Element-Binding Protein
Neuromuscular Junction
5' Flanking Region
Receptor Protein-Tyrosine Kinases
Transgenes
Muscle Cells
Small Interfering RNA
Mutation
DNA
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Inhibition of MuSK expression by CREB interacting with a CRE-like element and MyoD. / Kim, Chang Hoon; Xiong, Wencheng; Mei, Lin.

In: Molecular and Cellular Biology, Vol. 25, No. 13, 01.07.2005, p. 5329-5338.

Research output: Contribution to journalArticle

Kim, Chang Hoon ; Xiong, Wencheng ; Mei, Lin. / Inhibition of MuSK expression by CREB interacting with a CRE-like element and MyoD. In: Molecular and Cellular Biology. 2005 ; Vol. 25, No. 13. pp. 5329-5338.
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