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

Betina Macho; Stefano Brancorsini; Gian Maria Fimia; Mitsutoshi Setou; Nobutaka Hirokawa; Paolo Sassone-Corsi

doi:10.1126/science.1077265

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

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

Authors

Betina Macho¹, Stefano Brancorsini, Gian Maria Fimia, Mitsutoshi Setou, Nobutaka Hirokawa, Paolo Sassone-Corsi

Affiliation

¹ Institut de Génétique et de Biologie Moléculaire et Cellulaire, B. P. 10142, 67404 Illkirch, Strasbourg, France.

PMID: 12493914
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
Exportin 1 Protein
Fatty Acids, Unsaturated / pharmacology
Gene Expression Regulation, Developmental
Karyopherins / metabolism
Kinesins / chemistry
Kinesins / genetics
Kinesins / 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)
Cyclic AMP Response Element Modulator
Kinesins
leptomycin B