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 Golgi apparatus in animal cells breaks down at the onset of mitosis and is later rebuilt in the two daughter cells. Two AAA ATPases, NSF and p97/VCP, have been implicated in regulating membrane fusion steps that lead to regrowth of Golgi cisternae from mitotic fragments. NSF dissociates complexes of SNARE proteins, thereby reactivating them to mediate membrane fusion. However, NSF has a second function in regulating SNARE pairing together with the ubiquitin-like protein GATE-16. p97/VCP, on the other hand, is involved in a cycle of ubiquitination and deubiquitination of an unknown target that governs Golgi membrane dynamics. Here, these findings are reviewed and discussed in the context of the increasingly evident role of ubiquitin in membrane traffic processes.
 ...
PMID:Golgi reassembly after mitosis: the AAA family meets the ubiquitin family. 1603 55

The Golgi apparatus in animal cells breaks down at the onset of mitosis and is later rebuilt in the two daughter cells. Two AAA ATPases, NSF and p97/VCP, have been implicated in regulating membrane fusion steps that lead to regrowth of Golgi cisternae from mitotic fragments. NSF dissociates complexes of SNARE proteins, thereby reactivating them to mediate membrane fusion. However, NSF has a second function in regulating SNARE pairing together with the ubiquitin-like protein GATE-16. p97/VCP, on the other hand, is involved in a cycle of ubiquitination and deubiquitination of an unknown target that governs Golgi membrane dynamics. Here, these findings are reviewed and discussed in the context of the increasingly evident role of ubiquitin in membrane traffic processes.
 ...
PMID:Golgi reassembly after mitosis: the AAA family meets the ubiquitin family. 1587 10

Macroautophagy sequesters superflous cytosol and organelles into double-membraned autophagosomes. Over 30 autophagy-related (ATG) genes have been identified without elucidating the molecular details of autophagosome biogenesis. All proposed models for autophagosome formation require membrane fusion events (Fig. 1). Previous studies assumed that the autophagic machinery mediates these membrane fusions in a SNARE-independent manner and identified the ubiquitin-like protein Atg8 as a key component especially for elongation of the forming autophagosome. However, if and how Atg8 mediates membrane fusion and why a ubiquitin-like protein is needed for autophagosome biogenesis remained open questions. Since nuclear envelope growth and fusion of Golgi fragments are topologically similar to autophagosome formation and depend on the AAA (+) ATPase p97/VCP and p47 we analyzed the involvement of their yeast homologues Cdc48 and Shp1 in macroautophagy.
 ...
PMID:Cheating on ubiquitin with Atg8. 2115 Mar 10

To adapt quickly to the environmental change, bacteria have evolved a protein quality control (PQC) network to remove unwanted proteins. AAA + ( ATPases associated with diverse cellular activities) proteases form a major part of this PQC network, and the discovery of Pup ( prokaryotic ubiquitin-like protein ) -proteasome system revealed a novel mechanism of prokaryotic protein degradation. Proteolytic machines only degrade substrates bearing a degradation tag or degron to insure the proteolysis specificity. In addition, bacteria adopt different strategies to regulate the protein degradation. With the discovery of Ubiquitin-mediated protein degradation in eukaryotes, it has become evident that regulated protein degradation plays a crucial role in the cell response to environment change among eukaryotes and prokaryotes. Regulation by proteolysis has been shown to be involved in diverse bacterial cellular processes including growth, division, differentiation, pathogenesis and stress response. This review will focus on the structure, degradation process, and the function of AAA + proteolytic machines in bacteria.
 ...
PMID:[Proteolysis in bacteria--a review]. 2625 75

Apicomplexan parasites cause a variety of important infectious diseases, including malaria, toxoplasma encephalitis, and severe diarrhea due to Cryptosporidium Most apicomplexans depend on an organelle called the apicoplast which is derived from a red algal endosymbiont. The apicoplast is essential for the parasite as the compartment of fatty acid, heme, and isoprenoid biosynthesis. The majority of the approximate 500 apicoplast proteins are nucleus encoded and have to be imported across the four membranes that surround the apicoplast. Import across the second outermost membrane of the apicoplast, the periplastid membrane, depends on an apicoplast-specific endoplasmic reticulum-associated protein degradation (ERAD) complex and on enzymes of the associated ubiquitination cascade. However, identification of an apicoplast ubiquitin associated with this machinery has long been elusive. Here we identify a plastid ubiquitin-like protein (PUBL), an apicoplast protein that is derived from a ubiquitin ancestor but that has significantly changed in its primary sequence. PUBL is distinct from known ubiquitin-like proteins, and phylogenomic analyses suggest a clade specific to apicomplexans. We demonstrate that PUBL and the AAA ATPase CDC48AP both act to translocate apicoplast proteins across the periplastid membrane during protein import. Conditional null mutants and genetic complementation show that both proteins are critical for this process and for parasite survival. PUBL residues homologous to those that are required for ubiquitin conjugation onto target proteins are essential for this function, while those required for polyubiquitination and preprotein processing are dispensable. Our experiments provide a mechanistic understanding of the molecular machinery that drives protein import across the membranes of the apicoplast.IMPORTANCE Apicomplexan parasites are responsible for important human diseases. There are no effective vaccines for use in humans, and drug treatment faces multiple challenges, including emerging resistance, lack of efficacy across the lifecycle, and adverse drug effects. The apicoplast is a promising target for novel treatments: this chloroplast-like organelle is derived from an algal symbiont, is absent from the host, and is essential for parasite growth and pathogenesis. We use Toxoplasma gondii as a model to study the apicoplast due to its strong genetic tools and established functional assays. We identify a plastid ubiquitin-like protein (PUBL) which is a novel ubiquitin-like protein and demonstrate its importance and that of the motor protein CDC48AP for apicoplast protein import. These findings broaden our understanding of the evolution and mechanistic workings of a unique parasite organelle and may lead to new opportunities for treatments against important human pathogens.
 ...
PMID:A Plastid Protein That Evolved from Ubiquitin and Is Required for Apicoplast Protein Import in Toxoplasma gondii. 2865 25