Identification of FHOD1-binding proteins and mechanisms of FHOD1-regulated actin dynamics

Jennifer J. Westendorf, Sreenivas Koka

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Formin homology-2-domain containing protein 1 (FHOD1) regulates gene transcription, actin-cytoskeleton structure, and cell migration. To gain insight into the mechanisms by which FHOD1 mediates these diverse activities, a yeast-two-hybrid screen was performed to identify FHOD1-binding proteins. Three proteins specifically interacted with the carboxy-terminal two-thirds of FHOD1, which includes the FH1, FH2, and diaphanous activating domains (DAD). The newly identified FHOD1-binding proteins are protein kinase C binding protein 1 (PRKCBP1), cyclophilin B, and an isoform of WASP-interacting SH3-domain protein/diaphanous-interacting protein 1 (WISH/DIP1), named WISH-B. The proline-rich FH1 domain of FHOD1 was sufficient to interact with the central portion of PRKCP1 and full-length cyclophilin B. The FH1 domain also interacted with full-length WISH-B, but the extreme amino-terminus was sufficient to associate with WISH-B as well. WISH-B altered the solubility of FHOD1 in vitro and a truncation mutant containing the amino-terminal 227 residues of WISH-B disrupted FHOD1-induced stress fibers. WISH-B did not affect FHOD1-induced gene transcription through the serum response factor (SRF) recognition site on the skeletal α-actin promoter (SkA). However, stabilization of F-actin prevented FHOD1 dependent activation of this promoter in presence of high, but not low serum concentrations. Thus, the identification of a new FHOD1-binding protein provides insight into the mechanisms by which FHOD1 regulates actin polymerization and transcription.

Original languageEnglish (US)
Pages (from-to)29-41
Number of pages13
JournalJournal of cellular biochemistry
Volume92
Issue number1
DOIs
StatePublished - Dec 1 2004

Keywords

  • Cyclophilin B
  • DIP1
  • Diaphanous
  • FHOD1
  • FHOS
  • Formin
  • PRKCP1
  • RACK7
  • Stress fibers
  • WISH

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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