Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.4.4 (kinesin)
 5,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:CREM-dependent transcription in male germ cells controlled by a kinesin. 1249 14

The differentiation of male germ cell requires spermatogenic stage and cell-specific gene expression that is achieved by unique chromatin remodelling, transcriptional control, and the expression of testis-specific genes or isoforms. Specialized transcription complexes that coordinate the differentiation programme of spermatogenesis have been found in germ cells, which display specific differences in the components of the general transcription machinery. The TATA-binding (TBP) protein family and its associated co-factors, for example, show upregulated expression in testis. In this physiological context, transcriptional control mediated by the activator CREM represents an established paradigm. In somatic cells, activation by CREM requires its phosphorylation at a unique regulatory site (Ser117) and subsequent interaction with the ubiquitous coactivator CBP. In testis, CREM transcriptional activity is controlled through interaction with a tissue-specific partner, ACT, which confers a powerful, phosphorylation-independent activation capacity. The function of ACT is regulated by a testis-specific kinesin, KIF17b. This study discusses some aspects of the testis-specific transcription machinery, the function of which is essential for the process of spermatogenesis.
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PMID:A specific programme of gene transcription in male germ cells. 1515 9

Male germ cell differentiation requires a highly cell-specific gene expression programme that is achieved by unique chromatin remodelling, transcriptional control, and the expression of testis-specific genes or isoforms. The regulatory processes governing gene expression in spermatogenesis have fundamentally unique requirements, including meiosis, ongoing cellular differentiation and a peculiar chromatin organization. The signalling cascades and the downstream effectors contributing to the programme of spermatogenesis are currently being unravelled, revealing the unique features of germ cell regulatory circuits. This paper reports on the unique role that CREM exerts as a master regulator. Targeted inactivation of the genes encoding CREM and ACT has been achieved. ACT selectively associates with KIF17b, a kinesin motor protein highly expressed in germ cells. It has been found that KIF17b directly determines the intracellular localization of ACT. Thus, the activity of a transcriptional co-activator is intimately coupled to the function of a kinesin via tight regulation of its intracellular localization. The conservation of these elements and of their regulatory functions in human spermatogenesis indicates that they are likely to provide important insights into understanding the molecular mechanisms of human infertility.
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PMID:Genetic control of spermiogenesis: insights from the CREM gene and implications for human infertility. 1570 96

Spermatogenesis is a remarkably complex process in which diploid spermatogonial stem cells undergo a series of mitotic and meiotic cell divisions to give rise to haploid round spermatids. These haploid cells then go through a dramatic morphological remodelling involving extensive chromatin condensation, reduction in nuclear and cytoplasmic volume, formation of an acrosome system and tail, all of which contribute to the formation of a mature spermatozoon fully capable of fertilizing the oocyte and passing along its genetic information to the next generation. To accomplish such a complex program, an intricate and efficient mechanism is required to finely tune the levels of expression of specific genes necessary for this process. Accordingly, the regulation of gene expression in post-meiotic male germ cells is governed by specific mechanisms unique to these cells. The cyclic adenosine monophosphate (cAMP) response element modulator (CREM) is an essential component of this program, and its activity is regulated through interactions with a germ cell-specific, CREM phosphorylation-independent transcriptional co-activator, activator of CREM in testis (ACT). In turn, the ability of ACT to regulate CREM activity is controlled by a germ cell-specific kinesin, Kif17b, which regulates the subcellular distribution of ACT. Further, the mRNA from CREM target genes interacts with several germ cell-specific RNA-binding proteins, which function to transport and stabilize these mRNAs. This sophisticated and complex regulation of gene expression in post-meiotic germ cells is governed by unique mechanisms specific to these cells and is fundamental to male fertility.
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PMID:Regulation of gene expression in post-meiotic male germ cells: CREM-signalling pathways and male fertility. 1682 8