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)

Genes for the mitotic kinases Polo and Aurora A were first identified in Drosophila through screens of maternal effect lethal mutations for defects in spindle pole behaviour. These enzymes have been shown to be highly conserved and required for multiple functions in mitosis. Polo is stabilized at the centrosome by association with Hsp90. It is required for centrosome maturation on M-phase entry in order to recruit the gamma-tubulin ring complex and activate the abnormal spindle protein, Asp. These events facilitate the nucleation of minus ends of microtubules at the centrosome. The localization of Polo at the kinetochore and the mid-zone of the central spindle together with the phenotypes of polo mutants point to functions at the metaphase to anaphase transition and in cytokinesis. The latter are mediated, at least in part, through the Pavarotti kinesin-like motor protein and its conserved counterparts in other metazoans.
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PMID:Polo kinase and progression through M phase in Drosophila: a perspective from the spindle poles. 1564 Aug 38

Strains of uropathogenic Escherichia coli (UPEC) encode filamentous adhesive organelles called type 1 pili that promote bacterial colonization and invasion of the bladder epithelium. Type 1 pilus-mediated interactions with host receptors, including alpha3beta1 integrin, trigger localized actin rearrangements that lead to internalization of adherent bacteria via a zipper-like mechanism. Here we report that type 1 pilus-mediated bacterial invasion of bladder cells also requires input from host microtubules and histone deacetylase 6 (HDAC6), a cytosolic enzyme that, by deacetylating alpha-tubulin, can alter the stability of microtubules along with the recruitment and directional trafficking of the kinesin-1 motor complex. We found that disruption of microtubules by nocodazole or vinblastine treatment, as well as microtubule stabilization by taxol, inhibited host cell invasion by UPEC, as did silencing of HDAC6 expression or pharmacological inhibition of HDAC6 activity. Invasion did not require two alternate HDAC6 substrates, Hsp90 and cortactin, but was dependent upon the kinesin-1 light chain KLC2 and an upstream activator of HDAC6, aurora A kinase. These results indicate that HDAC6 and microtubules act as vital regulatory elements during the invasion process, possibly via indirect effects on kinesin-1 and associated cargos.
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PMID:Uropathogenic Escherichia coli invades host cells via an HDAC6-modulated microtubule-dependent pathway. 1899 40

Molecular chaperones are an essential group of proteins required to maintain proper protein homeostasis in the cell and include Hsp40, Hsp60, Hsp70, Hsp90, and Hsp100 among others. Hsp110 proteins form a subfamily of the Hsp70 family and seem to primarily function as nucleotide exchange factors for the Hsp70s. Data to date suggest that Hsp110 together with Hsp70 are required to ensure proper spindle assembly and nuclear distribution during cell division. More specifically, we propose that an Hsp110-Hsp70 complex modulates the activity and directionality of the kinesin-5 motor, Cin8, which is required for spindle elongation. The modulation of spindle length by molecular chaperones might be a mechanism by which cell division can be controlled especially under proteostatic stress.
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PMID:The control of spindle length by Hsp70 and Hsp110 molecular chaperones. 2343 84

Chaperones are critical for the folding and regulation of a wide array of cellular proteins. Heat Shock Proteins (Hsps) are the most representative group of chaperones. Hsp90 represents up to 1-2% of soluble protein. Although the Hsp90 role is being studied in neurodegenerative diseases, its role in neuronal differentiation remains mostly unknown. Since neuronal polarity mechanisms depend on local stability and degradation, we asked whether Hsp90 could be a regulator of axonal polarity and growth. Thus, we studied the role of Hsp90 activity in a well established model of cultured hippocampal neurons using an Hsp90 specific inhibitor, 17-AAG. Our present data shows that Hsp90 inhibition at different developmental stages disturbs neuronal polarity formation or axonal elongation. Hsp90 inhibition during the first 3h in culture promotes multiple axon morphology, while this inhibition after 3h slows down axonal elongation. Hsp90 inhibition was accompanied by decreased Akt and GSK3 expression, as well as, a reduced Akt activity. In parallel, we detected an alteration of kinesin-1 subcellular distribution. Moreover, these effects were seconded by changes in Hsp70/Hsc70 subcellular localization that seem to compensate the lack of Hsp90 activity. In conclusion, our data strongly suggests that Hsp90 activity is necessary to control the expression, activity or location of specific kinases and motor proteins during the axon specification and axon elongation processes. Even more, our data demonstrate the existence of a "time-window" for axon specification in this model of cultured neurons after which the inhibition of Hsp90 only affects axonal elongation mechanisms.
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PMID:Hsp90 activity is necessary to acquire a proper neuronal polarization. 2428 67

FKBP38 (FK506-binding protein 38), a membrane-anchored TPR (tetratricopeptide repeat)-containing immunophilin, regulates signalling pathways such as cell survival, apoptosis, proliferation and metastasis. However, the mechanisms that regulate the activity of FKBP38 are, at present, poorly understood. We previously reported that Ca2+/S100 proteins directly associate with the TPR proteins, such as Hop [Hsp70 (heat-shock protein of 70 kDa)/Hsp90-organizing protein], kinesin-light chain, Tom70 (translocase of outer mitochondrial membrane 70), FKBP52, CyP40 (cyclophilin 40), CHIP (C-terminus of Hsc70-interacting protein) and PP5 (protein phosphatase 5), leading to the dissociation of the interactions of the TPR proteins with their target proteins. Therefore we have hypothesized that Ca2+/S100 proteins can interact with FKBP38 and regulate its function. In vitro binding studies demonstrated that S100A1, S100A2, S100A6, S100B and S100P specifically interact with FKBP38 and inhibit the interaction of FKBP38 with Bcl-2 and Hsp90. Overexpression of permanently active S100P in Huh-7 cells inhibited the interaction of FKBP38 with Bcl-2, resulting in the suppression of Bcl-2 stability. The association of the S100 proteins with FKBP38 provides a Ca2+-dependent regulatory mechanism of the FKBP38-mediated signalling pathways.
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PMID:Ca2+/S100 proteins inhibit the interaction of FKBP38 with Bcl-2 and Hsp90. 2429 50