UPS / Ground state / Neuron degeneration / HYDROLASE
機能・相同性
機能・相同性情報
nuclear proteasome complex / Cross-presentation of soluble exogenous antigens (endosomes) / Proteasome assembly / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Regulation of ornithine decarboxylase (ODC) / Metalloprotease DUBs / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Autodegradation of Cdh1 by Cdh1:APC/C / SCF-beta-TrCP mediated degradation of Emi1 / APC/C:Cdc20 mediated degradation of Securin ...nuclear proteasome complex / Cross-presentation of soluble exogenous antigens (endosomes) / Proteasome assembly / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Regulation of ornithine decarboxylase (ODC) / Metalloprotease DUBs / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Autodegradation of Cdh1 by Cdh1:APC/C / SCF-beta-TrCP mediated degradation of Emi1 / APC/C:Cdc20 mediated degradation of Securin / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / SCF(Skp2)-mediated degradation of p27/p21 / Autodegradation of the E3 ubiquitin ligase COP1 / Asymmetric localization of PCP proteins / Degradation of DVL / Hedgehog ligand biogenesis / Dectin-1 mediated noncanonical NF-kB signaling / Degradation of GLI1 by the proteasome / Hedgehog 'on' state / TNFR2 non-canonical NF-kB pathway / NIK-->noncanonical NF-kB signaling / Assembly of the pre-replicative complex / CDK-mediated phosphorylation and removal of Cdc6 / G2/M Checkpoints / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Ubiquitin-dependent degradation of Cyclin D / The role of GTSE1 in G2/M progression after G2 checkpoint / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Regulation of RUNX3 expression and activity / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / GLI3 is processed to GLI3R by the proteasome / Activation of NF-kappaB in B cells / Degradation of beta-catenin by the destruction complex / Degradation of AXIN / UCH proteinases / Regulation of RAS by GAPs / Orc1 removal from chromatin / Neddylation / AUF1 (hnRNP D0) binds and destabilizes mRNA / MAPK6/MAPK4 signaling / Regulation of PTEN stability and activity / KEAP1-NFE2L2 pathway / Separation of Sister Chromatids / fluid transport / Antigen processing: Ubiquitination & Proteasome degradation / ABC-family proteins mediated transport / Ub-specific processing proteases / positive regulation of inclusion body assembly / thyrotropin-releasing hormone receptor binding / modulation by host of viral transcription / cytosolic proteasome complex / proteasome accessory complex / integrator complex / meiosis I / proteasome regulatory particle / proteasome-activating activity / proteasome regulatory particle, lid subcomplex / proteasome regulatory particle, base subcomplex / metal-dependent deubiquitinase activity / protein K63-linked deubiquitination / Neutrophil degranulation / proteasome core complex / proteasome binding / regulation of protein catabolic process / myofibril / proteasome storage granule / general transcription initiation factor binding / blastocyst development / immune system process / endopeptidase activator activity / NF-kappaB binding / proteasome endopeptidase complex / proteasome core complex, beta-subunit complex / proteasome assembly / threonine-type endopeptidase activity / proteasome core complex, alpha-subunit complex / mRNA export from nucleus / inclusion body / enzyme regulator activity / regulation of proteasomal protein catabolic process / TBP-class protein binding / proteasome complex / proteolysis involved in protein catabolic process / sarcomere / stem cell differentiation / lipopolysaccharide binding / negative regulation of inflammatory response to antigenic stimulus / P-body / double-strand break repair via homologous recombination / : / response to virus / double-strand break repair via nonhomologous end joining / nuclear matrix / metallopeptidase activity / positive regulation of NF-kappaB transcription factor activity / peptidase activity / ubiquitin-dependent protein catabolic process / cytoplasmic vesicle 類似検索 - 分子機能
ジャーナル: Cell / 年: 2018 タイトル: In Situ Structure of Neuronal C9orf72 Poly-GA Aggregates Reveals Proteasome Recruitment. 著者: Qiang Guo / Carina Lehmer / Antonio Martínez-Sánchez / Till Rudack / Florian Beck / Hannelore Hartmann / Manuela Pérez-Berlanga / Frédéric Frottin / Mark S Hipp / F Ulrich Hartl / Dieter ...著者: Qiang Guo / Carina Lehmer / Antonio Martínez-Sánchez / Till Rudack / Florian Beck / Hannelore Hartmann / Manuela Pérez-Berlanga / Frédéric Frottin / Mark S Hipp / F Ulrich Hartl / Dieter Edbauer / Wolfgang Baumeister / Rubén Fernández-Busnadiego / 要旨: Protein aggregation and dysfunction of the ubiquitin-proteasome system are hallmarks of many neurodegenerative diseases. Here, we address the elusive link between these phenomena by employing cryo- ...Protein aggregation and dysfunction of the ubiquitin-proteasome system are hallmarks of many neurodegenerative diseases. Here, we address the elusive link between these phenomena by employing cryo-electron tomography to dissect the molecular architecture of protein aggregates within intact neurons at high resolution. We focus on the poly-Gly-Ala (poly-GA) aggregates resulting from aberrant translation of an expanded GGGGCC repeat in C9orf72, the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. We find that poly-GA aggregates consist of densely packed twisted ribbons that recruit numerous 26S proteasome complexes, while other macromolecules are largely excluded. Proximity to poly-GA ribbons stabilizes a transient substrate-processing conformation of the 26S proteasome, suggesting stalled degradation. Thus, poly-GA aggregates may compromise neuronal proteostasis by driving the accumulation and functional impairment of a large fraction of cellular proteasomes.