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
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Amino Acid Sequence
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Animals
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COS Cells
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Cell Nucleus / metabolism
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Cyclic AMP Response Element Modulator
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Cytoplasm / metabolism
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DNA-Binding Proteins / metabolism
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Exportin 1 Protein
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Fatty Acids, Unsaturated / pharmacology
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Gene Expression Regulation, Developmental
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Karyopherins / metabolism
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Kinesins / chemistry
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Kinesins / genetics
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Kinesins / metabolism*
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LIM Domain Proteins
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Male
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Mice
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Molecular Motor Proteins / chemistry
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Molecular Motor Proteins / genetics
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Molecular Motor Proteins / metabolism*
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Molecular Sequence Data
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Promoter Regions, Genetic
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Protein Isoforms / chemistry
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Receptors, Cytoplasmic and Nuclear*
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Repressor Proteins*
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Spermatids / metabolism*
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Spermatogenesis*
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Testis / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription, Genetic*
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Transcriptional Activation
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Transfection
Substances
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DNA-Binding Proteins
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Fatty Acids, Unsaturated
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Fhl5 protein, mouse
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KIF17 protein, mouse
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Karyopherins
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LIM Domain Proteins
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Molecular Motor Proteins
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Protein Isoforms
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Receptors, Cytoplasmic and Nuclear
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Repressor Proteins
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Transcription Factors
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activator of CREM in testis (ACT)
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Cyclic AMP Response Element Modulator
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Kinesins
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leptomycin B