CREM-dependent transcription in male germ cells controlled by a kinesin

Science. 2002 Dec 20;298(5602):2388-90. doi: 10.1126/science.1077265.

Abstract

ACT is a LIM-only protein expressed exclusively in round spermatids, where it cooperates with transcriptional activator CREM in regulating various postmeiotic genes. Targeted inactivation of CREM leads to a complete block of mouse spermiogenesis. We sought to identify the regulatory steps controlling the functional interplay between CREM and ACT. We found that ACT selectively associates with KIF17b, a kinesin highly expressed in male germ cells. The ACT-KIF17b interaction is restricted to specific stages of spermatogenesis and directly determines the intracellular localization of ACT. Sensitivity to leptomycin B indicates that KIF17b can be actively exported from the nucleus through the Crm1 receptor. Thus, a kinesin directly controls the activity of a transcriptional coactivator by a tight regulation of its intracellular localization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Cell Nucleus / metabolism
  • Cyclic AMP Response Element Modulator
  • Cytoplasm / metabolism
  • DNA-Binding Proteins / metabolism
  • Fatty Acids, Unsaturated / pharmacology
  • Gene Expression Regulation, Developmental
  • Karyopherins / metabolism
  • Kinesin / chemistry
  • Kinesin / genetics
  • Kinesin / metabolism*
  • LIM Domain Proteins
  • Male
  • Mice
  • Molecular Motor Proteins / chemistry
  • Molecular Motor Proteins / genetics
  • Molecular Motor Proteins / metabolism*
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Receptors, Cytoplasmic and Nuclear*
  • Repressor Proteins*
  • Spermatids / metabolism*
  • Spermatogenesis*
  • Testis / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic*
  • Transcriptional Activation
  • Transfection

Substances

  • DNA-Binding Proteins
  • Fatty Acids, Unsaturated
  • Fhl5 protein, mouse
  • KIF17 protein, mouse
  • Karyopherins
  • LIM Domain Proteins
  • Molecular Motor Proteins
  • Protein Isoforms
  • Receptors, Cytoplasmic and Nuclear
  • Repressor Proteins
  • Transcription Factors
  • activator of CREM in testis (ACT)
  • exportin 1 protein
  • Cyclic AMP Response Element Modulator
  • Kinesin
  • leptomycin B