Disease relevance of Khdrbs1

• Cell death, as determined by measuring the loss of blue cells, was observed in AT3 cells transfected with 6K plus E1 and with P62 but not in cells transfected with capsid [1].
• Genes encoding the three structural proteins--capsid, the precursor E1 (6K plus E1), and the precursor E2 (P62 or E3 plus E2)--were cotransfected with a beta-galactosidase reporter plasmid in transient-transfection assays in rat prostate adenocarcinoma AT3 cells [1].
• Modifications in P62 occur due to proteasome inhibition in alcoholic liver disease [2].
• Immunostaining of hepatocytes from human liver with alcoholic hepatitis showed colocalization of ubiquitin and P62 in Mallory bodies [2].

High impact information on Khdrbs1

• Furthermore, p68 is the HSP70 heat shock protein cognate, found in elevated levels in a p53-overproducing cell line [3].
• Additional neurotypic proteins altered by TMT-induced injury included one of the neurofilament (NF) triplet proteins (p68) and a protein with the electrophoretic characteristics of neuron-specific enolase (NSE) [4].
• GFP-Sam68 invaded the dendrites after 2 hours with high KCl, and returned to the nucleus within 3 hours after termination of the KCl treatment [5].
• No significant change was observed in the phosphorylation of Sam68 after depolarization [5].
• Translocation of Sam68 to the distal dendrites was microtubule dependent [5].

Biological context of Khdrbs1

• Furthermore, inhibition of CRM-1-mediated nuclear export by leptomycin B partially prevented the depolarization-induced nuclear efflux of GFP-Sam68 [5].
• Deletion mutagenesis of P62 indicated that large regions of the cytoplasmic domain and extracellular domain were not essential for the induction of cell death [1].
• The role of Sam68, an RNA binding protein and putative substrate of the insulin receptor (IR) in insulin signaling was studied using CHO wild type (WT) cells, CHO cells overexpressing IR, and rat white adipocytes as a physiological system [6].
• The expression of Sam68, a protein involved in insulin signal transduction, is enhanced by insulin stimulation [6].
• Alternative splicing gives rise to two forms of the p68 Ca2(+)-binding protein [7].

Anatomical context of Khdrbs1

• Somatodendritic localization and mRNA association of the splicing regulatory protein Sam68 in the hippocampus and cortex [8].
• Sam68 extracted from the synaptosomal fraction cosedimented with polysomes on sucrose gradients [8].
• Insulin stimulation for 16 h enhanced the expression of Sam68 in rat adipocytes and CHO-IR cells [6].
• Ang II also caused a time- and dose-dependent stimulation of P62 phosphorylation, a glycoprotein of the nuclear pore complex [9].
• Here we show that NIH3T3 murine fibroblasts transformed by p21-HA-C-RAS or pp60-V-SRC oncoproteins have markedly reduced levels of p68-MARCKS and that most of the remaining MARCKS protein is found in the cytosol [10].

Associations of Khdrbs1 with chemical compounds

• When present, the dendritic GFP-Sam68 formed granules, 26% of which were colocalized with ethidium bromide-stained RNA clusters [5].
• In CHO-IR cells and adipocytes, Sam68 was tyrosine phosphorylated in response to insulin, and then associated with p85 phosphatidylinositol-3 kinase along with IRS-1 [6].
• FAK with phosphorylation on serine 722 colocalized with Sam68 but not fibrillarin [11].
• Rats fed ethanol chronically and their controls showed that P62 is colocalized with the proteasome in hepatocytes as shown by confocal microscopy [2].
• P62 protein levels were also increased in the purified proteasome fraction of rats given PS-341 [2].

Other interactions of Khdrbs1

• On the contrary, FRNK phosphorylated on 217 coexisted with fibrillarin but not Sam68 [11].

Analytical, diagnostic and therapeutic context of Khdrbs1

• A combination of immunoprecipitation and RT-PCR directly confirmed that Sam68 was bound to polyadenylated mRNA in cortical lysates [8].
• In electrophoretic mobility shift assays, recombinant GST-Sam68 as well as brain-derived Sam68 bound with high affinity to the alphaCaMKII 3' untranslated region [8].
• We show here that an antiserum directed against a synthetic peptide corresponding to the region containing the splice sequence, recognises only the upper band of the p68 doublet by both immunoprecipitation and Western blotting [7].
• To verify the observed changes, quantitative PCR and in situ hybridization were performed for three fragments representing proteins with quite different functions (GluR2-flop, SC1, and p68 RNA helicase) [12].
• Their anxiety-like behavior was evaluated using an elevated plus-maze at P62, and then NPY immunohistochemistry in the basolateral amygdala (BLA) was performed [13].

References