Ubiquitin Activation and Transfer Process

CHIP = U-box type E3 ligase that interacts with HSP70 and HSP90 through its TPR domains E3 = Facilitates transfer of ubiquitin to the substrate protein, usually a lysine side-chain Stub1 = Encoded by the CHIP gene and mediates substrate protein ubiquitination LRRK = A protein that interacts with CHIP and is targeted for degradation or aggregation

HSP70 = Prevents further aggregation of oligomeric 𝛂–synuclein HSP90 = Involved in later stages of protein folding Hop = Acts as a 'holdase'

HSP70 = Interacts with CHIP through its EEVD motifs HSP90 = Interacts with CHIP through its TPR domains HSP40 = Encoded by the STUB1 gene and mediates protein folding DNAJ = A protein that interacts with HSP70 and facilitates protein folding

<p>Intrinsically disordered proteins = Requires a cofactor or ligand to fold Glucocorticoid receptor = Contains a disordered region Damaged proteins = Cannot fold due to oxidation or cleavage Androgen receptor = Needs a cofactor or ligand to fold</p> Signup and view all the answers

<p>HSP70-Hop-HSP90 complex = Involved in protein degradation HSP70-Hop complex = Acts early in the protein folding pathway HSP90-Hop complex = Acts as a 'holdase'</p> Signup and view all the answers

<p>Alzheimer's disease = Tau and APP Parkinson's disease = α-synuclein Huntington's disease = Huntingtin (HTT) Amyotrophic lateral sclerosis = Superoxide dismutase-1 (SOD1)</p> Signup and view all the answers

<p>E1 = Activates ubiquitin in an ATP-dependent reaction E2 = Transfers ubiquitin to the catalytic cysteine by transthiolation E3 = Facilitates transfer of ubiquitin to the substrate protein, usually a lysine side-chain Ubiquitin = Forms an isopeptide bond with the substrate protein</p> Signup and view all the answers

<p>EEVD motif = HSP70 LTPTLVSLL = Hop SIVPAT = HSP90 EVIEPE = HSP90</p> Signup and view all the answers

<p>Ubiquitin-proteasome system = Dependent on ubiquitination Lysine-linked polyubiquitination = Involved in protein degradation Ubiquitination-dependent degradation = Involves E3 ligase mechanisms HSP70-Hop-HSP90 complex = Prevents protein aggregation</p> Signup and view all the answers

<p>Lys63 = Facilitates protein aggregation and binding to ubiquitin-bindng proteins Lys27 = Targets proteins for degradation by the proteasome Lys48 = Not mentioned in the context Lys29 = Not mentioned in the context</p> Signup and view all the answers

<p>Protein misfolding = Can lead to aggregation and degradation Failure of protein folding machinery = Can result in damaged proteins Intrinsic disorder = Can lead to protein degradation Mutant proteins = Can lead to protein misfolding</p> Signup and view all the answers

<p>p53 = Cancer Ataxin-1 = Spinocerebellar ataxia Ataxin-3 = Spinocerebellar ataxia PTEN-induced putative kinase-1 (PINK1) = Parkinson's disease</p> Signup and view all the answers

<p>FBXL7 = Alzheimer's disease FBXO7 (PARK15) = Parkinson's disease RNF216/TRIAD3 = Frontotemporal dementia LRSAM1 = Amyotrophic lateral sclerosis</p> Signup and view all the answers

<p>DNAJB1 = Fibrolamellar hepatocellular carcinoma DNAJC5 = Distal hereditary motor neuropathy DNAJB2 = Early-onset obesity, mental retardation and epilepsy DNAJC6 = Charcot Marie Tooth disease type 2</p> Signup and view all the answers

<p>CCNF = Alzheimer's disease RNF170 = Autosomal-dominant sensory ataxia TRIM2 = Gordon Holmes syndrome UBE3C = Charcot-Marie-Tooth Type 2/Axonal neuropathy</p> Signup and view all the answers

<p>DNAJB5 = Hyperphenylalaninemia, mild, non-BH4 deficient DNAJC17 = Primary ciliary dyskinesia type 34 DNAJC12 = Hereditary myoclonus and progressive distal muscular atrophy DNAJC19 = Combined cerebellar and peripheral ataxia with hearing loss and diabetes mellitus</p> Signup and view all the answers

<p>PARK2 = Parkinson's disease FBXL13 = Frontotemporal dementia LRSAM1 = Episodic ataxia type 8 STUB1 = Distal hereditary motor neuropathy</p> Signup and view all the answers

<p>DNAJC3 = Bone marrow failure syndrome type 3 DNAJC21 = Autosomal recessive spastic ataxia of Charlevoix-Saguenay DNAJC29 = Zarouchlioti et al 2018 DNAJC11 = Hereditary myoclonus and progressive distal muscular atrophy</p> Signup and view all the answers