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)

Using a genetic strategy designed to find proteins involved in the function of the Saccharomyces cerevisiae transcriptional activator GAL4, we isolated mutants in two genes which rescue a class of gal4 activation domain mutants. One of these genes, SUG1, encodes a member of a large family of putative ATPases, the Conserved ATPase containing Domain (CAD) proteins (also known as AAA proteins) that are involved in a wide variety of cellular functions. Subsequently, SUG1 was identified as a subunit of the 26 S proteasome. We have now cloned the gene defined by the second complementation group. SUG2 encodes an essential 49-kDa protein that is also a member of the CAD family and is 43% identical to SUG1. The mutation in sug2-1, like that in sug1-1, is found in the CAD near the highly conserved ATPase motif. We present biochemical and genetic evidence that SUG2 is associated in vivo with SUG1 and is a novel CAD protein subunit of the 26 S proteasome. With its highly conserved mammalian homologs, human p42 and ground squirrel CADp44, SUG2 defines a new class of proteasomal CAD proteins.
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PMID:Isolation and characterization of SUG2. A novel ATPase family component of the yeast 26 S proteasome. 895 18

Smallminded (smid) encodes a new member of the cdc48p/VCP subfamily of AAA proteins in Drosophila. The gene was isolated by plasmid rescue from a GAL4 enhancer trap line which shows reporter gene expression in neuroblasts, imaginal disks and a subset of sensory neurons. Larvae homozygous for the insert arrest development as second instar larvae and die without pupating. The most obvious defect in these larvae is a significantly reduced CNS, hence the naming of the gene as smallminded. The deduced amino acid sequence of smid contains a tandem duplication of the AAA nucleotide binding domain characteristic of the cdc48p/VCP subfamily. Overall, smid shares 33% identical residues with its closest relative, yeast L0919-chrXII and 26-29% with other members of the cdc48p/VCP subfamily. The most highly conserved regions of the predicted protein structure are found in and around the nucleotide binding domains. The gene is expressed at all developmental stages.
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PMID:Isolation and characterisation of smallminded, a Drosophila gene encoding a new member of the Cdc48p/VCP subfamily of AAA proteins. 952 63

Interactions with co-factors provide a means by which HOX proteins exert specificity. To identify candidate protein interactors of HOXA13, we created and screened an E11.5-E12.5, distal limb bud yeast two-hybrid prey library. Among the interactors, we isolated the BMP-signaling effector Smad5, which interacted with the paralogous HOXD13 but not with HOXA11 or HOXA9, revealing unique interaction capabilities of the AbdB-like HOX proteins. Using deletion mutants, we determined that the MH2 domain of Smad5 is necessary for HOXA13 interaction. This is the first report demonstrating an interaction between HOX proteins and the MH2 domain of Smad proteins. HOXA13 and HOXD13 also bind to other BMP and TGF-beta/Activin-regulated Smad proteins including Smad1 and Smad2, but not Smad4. Furthermore, HOXD13 could be co-immunoprecipitated with Smad1 from cells. Expression of HOXA13, HOXD13 or a HOXD13 homeodomain mutant (HOXD13(IQN>AAA)) antagonized TGF-beta-stimulated transcriptional activation of the pAdtrack-3TP-Lux reporter vector in Mv1Lu cells as well as the Smad3/Smad4-activated pTRS6-E1b promoter in Hep3B cells. Finally, using mammalian one-hybrid assay, we show that transcriptional activation by a GAL4/Smad3-C-terminus fusion protein is specifically inhibited by HOXA13. Our results identify a new co-factor for HOX group 13 proteins and suggest that HOX proteins may modulate Smad-mediated transcriptional activity through protein-protein interactions without the requirement for HOX monomeric DNA-binding capability.
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PMID:Group 13 HOX proteins interact with the MH2 domain of R-Smads and modulate Smad transcriptional activation functions independent of HOX DNA-binding capability. 1608 34