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

The scaffold protein p62 is involved in internalization and trafficking of TrkA. The receptor is deubiquitinated by the proteasomes prior to degradation by lysosomes. Here we demonstrate that p62 serves as a shuttling protein for interaction of ubiquitinated TrkA with Rpt1, one of the six ATPases of 19S regulatory particle of the 26S proteasome. In p62(-/-) mouse brain TrkA failed to interact with the Rpt1. The interaction of TrkA with Rpt1 was reduced in proteasomes isolated from p62(-/-) brain, but was restored by addition of p62. The UBA domain of p62 interacts with TrkA and its PB1/UbL domain with AAA-ATPase cassette in the C-terminal region of Rpt1. Last, neurotrophin-dependent turnover of TrkA was impaired by reduction in the level of p62. These findings reveal that p62 serves as a shuttling factor for interaction of ubiquitinated substrates with the proteasome and could promote localized protein turnover in neurons.
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PMID:p62 serves as a shuttling factor for TrkA interaction with the proteasome. 1859 72

Abdominal aortic aneurysm (AAA) is a lethal disease, occurring mostly in men more than 65 years of age. Until recently, the pathogenesis of AAA remains poorly understood. MicroRNAs (miRNAs) are a novel class of endogenous small non-coding RNAs that play important roles in diverse biological and pathological processes including cardiovascular diseases. However, their biological roles in AAA formation have not been elucidated. In this study, we employed oligonucleotide microarrays to detect and compare miRNA expression profiles in a rat model of AAA. The abdominal aorta was exposed and incubated for 20 min with saline supplemented with calcium chloride and collagenase. After 28 days, the treated aortas were evaluated by digital measurement and angiography. A 50% increase over the normal diameter is considered as AAA. Our results revealed a set of differentially expressed miRNAs, with 10 significantly up-regulated and 5 significantly down-regulated miRNAs in AAA tissues. Four miRNAs (miR-19a, miR-19b, miR-132, and miR-221) were randomly selected for validation using real-time RT-PCR. Functional annotations of all putative targets of differentially expressed miRNAs via bioinformatics approaches revealed that predicted targets were highly enriched and involved in several key signaling pathways important for AAA formation, including pathways in cancer and signaling pathways involving mitogen-activated protein kinase, Wnt, neurotrophin, and ErbB. In summary, this study indicates that miRNAs might contribute to AAA formation probably by affecting multiple target genes and signaling pathways, which is expected to provide new clues to develop targeted therapies against this calamitous disease.
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PMID:Identification and characteristics of microRNAs with altered expression patterns in a rat model of abdominal aortic aneurysms. 2103 Aug 19