CREM-dependent transcription in male germ cells controlled by a kinesin.
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.
Macho
Betina
B
Institut de Génétique et de Biologie Moléculaire et Cellulaire, B. P. 10142, 67404 Illkirch, Strasbourg, France.
Brancorsini
Stefano
S
Fimia
Gian Maria
GM
Setou
Mitsutoshi
M
Hirokawa
Nobutaka
N
Sassone-Corsi
Paolo
P
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D051786:Cyclic AMP Response Element Modulator; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D028884:Karyopherins / Q000378:metabolism; D016547:Kinesins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D060588:LIM Domain Proteins; D008297:Male; D051379:Mice; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D013087:Spermatids / Q000378:metabolism*; D013091:Spermatogenesis; D013737:Testis / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D000097606:Exportin 1 Protein
D051786:Cyclic AMP Response Element Modulator; D004268:DNA-Binding Proteins; D005231:Fatty Acids, Unsaturated; D028884:Karyopherins; D016547:Kinesins; D060588:LIM Domain Proteins; D020409:Molecular Motor Proteins; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D014157:Transcription Factors; D000097606:Exportin 1 Protein; C504657:Fhl5 protein, mouse; C409642:KIF17 protein, mouse; C117930:activator of CREM in testis (ACT); C038753:leptomycin B