Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heat shock transcription factor 1 (HSF1) is the main regulator of the stress response that triggers the transcription of several genes encoding heat shock proteins (Hsps). Hsps act as molecular chaperones involved in protein folding, stability, and trafficking. HSF1 is highly expressed in oocytes and Hsf1 knock-out in mice revealed that in the absence of stress this factor plays an important role in female reproduction. We previously reported that Hsf1(-/-) females produce oocytes but no viable embryos. Consequently, we asked whether oocytes require HSF1 to regulate a particular set of Hsps necessary for them to develop. We find that Hsp90alpha (Hspaa1) is the major HSF1-dependent chaperone inasmuch as Hsf1 knock-out resulted in Hsp90-depleted oocytes. These oocytes exhibited delayed germinal vesicle breakdown (or G(2)/M transition), partial meiosis I block, and defective asymmetrical division. To probe the role of Hsp90alpha in this meiotic syndrome, we analyzed meiotic maturation in wild-type oocytes treated with a specific inhibitor of Hsp90, 17-allylamino-17-demethoxy-geldanamycin, and observed similar defects. At the molecular level we showed that, together with these developmental anomalies, CDK1 and MAPK, key meiotic kinases, were significantly disturbed. Thus, our data demonstrate that HSF1 is a maternal transcription factor essential for normal progression of meiosis.
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PMID:Mammalian heat shock factor 1 is essential for oocyte meiosis and directly regulates Hsp90alpha expression. 1915 73

The wealth of neurons that make up the brain are generated through the proliferative activity of neural stem cells during development. This neurogenesis activity involves complex cell cycle control of proliferative self-renewal, differentiation, and termination processes in these cells. Considerable progress has been made in understanding these processes in the neural stem cell-like neuroblasts which generate the brain in the genetic model system Drosophila. Neuroblasts in the developing fly brain generate neurons through repeated series of asymmetrical cell divisions, which balance self-renewal of the neuroblast with generation of differentiated progeny through the segregation of cell fate determinants such as Numb, Prospero, and Brat to the neural progeny. A number of classical cell cycle regulators such as cdc2/CDK1, Polo, Aurora A, and cyclin E are implicated in the control of asymmetric divisions in neuroblasts linking the cell cycle to the asymmetrical division machinery. The cellular and molecular identity of the postmitotic neurons produced by proliferating neuroblasts is influenced by the timing of their exit from the cell cycle through the action of a temporal expression series of transcription factors, which include Hunchback, Kruppel, Pdm, and Castor. This temporal series is also implicated in the control of termination of neuroblast proliferation which is effected by two different cell cycle exit strategies, terminal differentiative division or programmed cell death of the neuroblast. Defects in the asymmetric division machinery which interfere with the termination of proliferation can result in uncontrolled tumorigenic overgrowth. These findings in Drosophila brain development are likely to have general relevance in neural stem cell biology and may apply to cell cycle control in mammalian brain development as well.
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PMID:Drosophila neural stem cells: cell cycle control of self-renewal, differentiation, and termination in brain development. 2163 Jan 58