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)

The development of highly asymmetrical neurones from undifferentiated neuroblasts involves the extension of processes (axon and dendrites), that depends on the assembly of an inner microtubule scaffolding. Clonal cell lines of neuronal origin, N2A and NIE-115 neuroblastoma cells, have been chosen as model systems to study the modifications of microtubule protein which accompany the outgrowth of axon-like processes (neurites). Neuroblastoma cells grow as proliferating and undifferentiated cells in standard culture medium but can be considered as committed neuronal precursors. Thus, they are characterized by a high content of tubulin, including the minor neuronal-specific beta 3 isoform, and of MAPs including MAP1B and tau-like proteins. Serum withdrawal from the culture medium results in the extension of axon-like processes which is paralleled by a net increase in the amount of assembled tubulin. However, there is not any increase in the total amount of either tubulin or major MAPs which suggests an involvement of other regulatory factors in the promotion of microtubule assembly. Of relevance in this respect is the fact that beta 3-tubulin, MAP1B, and tau-like proteins become phosphorylated during neurite extension. A casein kinase II-like enzyme may be involved in some of these phosphorylation events. This enzyme is primarily localized to the nuclei in undifferentiated neuroblastoma cells, whereas a wider distribution of the enzyme between the nucleus and the cytoplasm is found in differentiating neuroblastoma cells. It thus appears plausible that a modified sorting of casein kinase II into the nucleus and the cytoplasm may be involved in the triggering of the phosphorylation of microtubule proteins during neuroblastoma cell differentiation.
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PMID:Microtubule protein phosphorylation in neuroblastoma cells and neurite growth. 182 7

Integration of genome-wide profiles of DNA copy number alterations (CNAs) and gene expression variations (GEVs) could provide combined power to the identification of driver genes and gene networks in tumors. Here we merge matched genome and transcriptome microarray analyses from neuroblastoma samples to derive correlation patterns of CNAs and GEVs, irrespective of their genomic location. Neuroblastoma correlation patterns are strongly asymmetrical, being on average 10 CNAs linked to 1 GEV, and show the widespread prevalence of long range covariance. Functional enrichment and network analysis of the genes covarying with CNAs consistently point to a major cell function, the regulation of mitotic spindle assembly. Moreover, elevated expression of 14 key genes promoting this function is strongly associated to high-risk neuroblastomas with 1p loss and MYCN amplification in a set of 410 tumor samples (P < 0.00001). Independent CNA/GEV profiling on neuroblastoma cell lines shows that increased levels of expression of these genes are linked to 1p loss. By this approach, we reveal a convergence of clustered neuroblastoma CNAs toward increased expression of a group of prognostic and functionally cooperating genes. We therefore propose gain of function of the spindle assembly machinery as a lesion potentially offering new targets for therapy of high-risk neuroblastoma.
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PMID:Segmental chromosome aberrations converge on overexpression of mitotic spindle regulatory genes in high-risk neuroblastoma. 2233 47