A novel role for DYX1C1, a chaperone protein for both Hsp70 and Hsp90, in breast cancer

J Cancer Res Clin Oncol. 2009 Sep;135(9):1265-76. doi: 10.1007/s00432-009-0568-6. Epub 2009 Mar 11.

Abstract

Aims: With three consecutive tetratricopeptide repeat (TPR) motifs at its C-terminus essential for neuronal migration, and a p23 domain at its N-terminus, DYX1C1 was the first gene proposed to have a role in developmental dyslexia. In this study, we attempted to identify the potential interaction of DYX1C1 and heat shock protein, and the role of DYX1C1 in breast cancer.

Main methods: GST pull-down, a yeast two-hybrid system, RT-PCR, site-directed mutagenesis approach.

Key findings: Our study initially confirmed DYX1C1, a dyslexia related protein, could interact with Hsp70 and Hsp90 via GST pull-down and a yeast two-hybrid system. And we verified that EEVD, the C-terminal residues of DYX1C1, is responsible for the identified association. Further, DYX1C1 mRNA was significantly overexpressed in malignant breast tumor, linking with the up-regulated expression of Hsp70 and Hsp90.

Significance: These results suggest that DYX1C1 is a novel Hsp70 and Hsp90-interacting co-chaperone protein and its expression is associated with malignancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cytoskeletal Proteins
  • Female
  • HSP70 Heat-Shock Proteins / metabolism*
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Two-Hybrid System Techniques
  • Up-Regulation / genetics

Substances

  • Cytoskeletal Proteins
  • DNAAF4 protein, human
  • HSP70 Heat-Shock Proteins
  • HSP90 Heat-Shock Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • RNA, Messenger