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Altered Twist1 and Hand2 dimerization is associated with Saethre-Chotzen syndrome and limb abnormalities.

Publication ,  Journal Article
Firulli, BA; Krawchuk, D; Centonze, VE; Vargesson, N; Virshup, DM; Conway, SJ; Cserjesi, P; Laufer, E; Firulli, AB
Published in: Nat Genet
April 2005

Autosomal dominant mutations in the gene encoding the basic helix-loop-helix transcription factor Twist1 are associated with limb and craniofacial defects in humans with Saethre-Chotzen syndrome. The molecular mechanism underlying these phenotypes is poorly understood. We show that ectopic expression of the related basic helix-loop-helix factor Hand2 phenocopies Twist1 loss of function in the limb and that the two factors have a gene dosage-dependent antagonistic interaction. Dimerization partner choice by Twist1 and Hand2 can be modulated by protein kinase A- and protein phosphatase 2A-regulated phosphorylation of conserved helix I residues. Notably, multiple Twist1 mutations associated with Saethre-Chotzen syndrome alter protein kinase A-mediated phosphorylation of Twist1, suggesting that misregulation of Twist1 dimerization through either stoichiometric or post-translational mechanisms underlies phenotypes of individuals with Saethre-Chotzen syndrome.

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Published In

Nat Genet

DOI

ISSN

1061-4036

Publication Date

April 2005

Volume

37

Issue

4

Start / End Page

373 / 381

Location

United States

Related Subject Headings

  • Zebrafish Proteins
  • Twist-Related Protein 1
  • Transcription Factors
  • Sequence Homology, Amino Acid
  • Protein Phosphatase 2
  • Phosphorylation
  • Phosphoprotein Phosphatases
  • Phenotype
  • Nuclear Proteins
  • Mutation
 

Citation

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Firulli, B. A., Krawchuk, D., Centonze, V. E., Vargesson, N., Virshup, D. M., Conway, S. J., … Firulli, A. B. (2005). Altered Twist1 and Hand2 dimerization is associated with Saethre-Chotzen syndrome and limb abnormalities. Nat Genet, 37(4), 373–381. https://doi.org/10.1038/ng1525
Firulli, Beth A., Dayana Krawchuk, Victoria E. Centonze, Neil Vargesson, David M. Virshup, Simon J. Conway, Peter Cserjesi, Ed Laufer, and Anthony B. Firulli. “Altered Twist1 and Hand2 dimerization is associated with Saethre-Chotzen syndrome and limb abnormalities.Nat Genet 37, no. 4 (April 2005): 373–81. https://doi.org/10.1038/ng1525.
Firulli BA, Krawchuk D, Centonze VE, Vargesson N, Virshup DM, Conway SJ, et al. Altered Twist1 and Hand2 dimerization is associated with Saethre-Chotzen syndrome and limb abnormalities. Nat Genet. 2005 Apr;37(4):373–81.
Firulli, Beth A., et al. “Altered Twist1 and Hand2 dimerization is associated with Saethre-Chotzen syndrome and limb abnormalities.Nat Genet, vol. 37, no. 4, Apr. 2005, pp. 373–81. Pubmed, doi:10.1038/ng1525.
Firulli BA, Krawchuk D, Centonze VE, Vargesson N, Virshup DM, Conway SJ, Cserjesi P, Laufer E, Firulli AB. Altered Twist1 and Hand2 dimerization is associated with Saethre-Chotzen syndrome and limb abnormalities. Nat Genet. 2005 Apr;37(4):373–381.

Published In

Nat Genet

DOI

ISSN

1061-4036

Publication Date

April 2005

Volume

37

Issue

4

Start / End Page

373 / 381

Location

United States

Related Subject Headings

  • Zebrafish Proteins
  • Twist-Related Protein 1
  • Transcription Factors
  • Sequence Homology, Amino Acid
  • Protein Phosphatase 2
  • Phosphorylation
  • Phosphoprotein Phosphatases
  • Phenotype
  • Nuclear Proteins
  • Mutation