Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mouse SKD1 is an AAA-type ATPase homologous to the yeast Vps4p implicated in transport from endosomes to the vacuole. To elucidate a possible role of SKD1 in mammalian endocytosis, we generated a mutant SKD1, harboring a mutation (E235Q) that is equivalent to the dominant negative mutation (E233Q) in Vps4p. Overexpression of the mutant SKD1 in cultured mammalian cells caused defect in uptake of transferrin and low-density lipoprotein. This was due to loss of their receptors from the cell surface. The decrease of the surface transferrin receptor (TfR) was correlated with expression levels of the mutant protein. The mutant protein displayed a perinuclear punctate distribution in contrast to a diffuse pattern of the wild-type SKD1. TfR, the lysosomal protein lamp-1, endocytosed dextran, and epidermal growth factor but not markers for the secretory pathway were accumulated in the mutant SKD1-localized compartments. Degradation of epidermal growth factor was inhibited. Electron microscopy revealed that the compartments were exaggerated multivesicular vacuoles with numerous tubulo-vesicular extensions containing TfR and endocytosed horseradish peroxidase. The early endosome antigen EEA1 was also redistributed to these aberrant membranes. Taken together, our findings suggest that SKD1 regulates morphology of endosomes and membrane traffic through them.
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PMID:The mouse SKD1, a homologue of yeast Vps4p, is required for normal endosomal trafficking and morphology in mammalian cells. 1067 28

The chaperone-related, ubiquitin-selective AAA (ATPase associated with a variety of cellular activities) protein Cdc48 (also known as TER94, p97 and VCP) is a key regulator of intracellular proteolysis in eukaryotes. It uses the energy derived from ATP hydrolysis to segregate ubiquitylated proteins from stable assemblies with proteins, membranes and chromatin. Originally characterized as essential factor in proteasomal degradation pathways, Cdc48 was recently found to control lysosomal protein degradation as well. Moreover, impaired lysosomal proteolysis due to mutational inactivation of Cdc48 causes protein aggregation diseases in humans. This review introduces the major systems of intracellular proteolysis in eukaryotes and the role of protein ubiquitylation. It then discusses in detail structure, mechanism and cellular functions of Cdc48 with an emphasis on protein degradation pathways in yeast.
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PMID:Roles of Cdc48 in regulated protein degradation in yeast. 2347 42