ⓘ PSMD6

                                     

ⓘ PSMD6

The proteasome and its subunits are of clinical significance for at least two reasons: 1 a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, and 2 they can be exploited as drug targets for therapeutic interventions. More recently, more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathophysiology of the proteasome should lead to clinical applications in the future.

In proteasomes form a key component of the ubiquitin-Proteasomal UPS system and the corresponding cellular protein quality control PQC. Protein ubiquitination and subsequent proteolysis and degradation via proteasome are important mechanisms in the regulation of cell cycle, growth and cell differentiation and gene transcription, signal transmission and apoptosis. Subsequently, under the threat of proteasomal complex Assembly and function lead to reduced proteolytic activity and accumulation of damaged or incorrectly folded proteins. The accumulation of such proteins may contribute to the pathogenesis and phenotypic characteristics of neurodegenerative diseases, cardiovascular diseases, inflammatory reactions and autoimmune diseases and systemic reactions to DNA damage, leading to the development of malignant tumors.

Numerous experimental and clinical studies have shown that aberrations and dysregulation of the UPS contribution to the pathogenesis of neurodegenerative and myodegenerative disorders, including Alzheimers disease, Parkinsons Disease, and picks disease, amyotrophic lateral sclerosis als, Huntingtons disease, Creutzfeldt–Jakob disease and a disease of neurons, polyglutamine Poly-Q diseases, muscular dystrophy and some rare forms of neurodegenerative diseases associated with dementia. In the framework of the ubiquitin-Proteasomal system, the UPS, the proteasome maintains homeostasis cardiac protein and thus plays an important role in cardiac ischemic damage, hypertrophy of the ventricle and congestive heart failure. In addition, accumulated evidence that the UPS plays an important role in malignant transformation. Proteolysis of the Windows plays an important role in the response of cancer cells to stimulatory signals that are critical for cancer development. Accordingly, gene expression of the degradation of transcription factors such as p53, C-Jun and C-FOS in the, NF-KB, C-MYC, HIF-1α, MATa2, STAT3, Sterol-regulated element-binding proteins and androgen receptor are controlled by UPS and are thus involved in the development of various malignancies. Moreover, the UPS regulates the degradation products of tumor suppressor genes such as adenomatous polyposis coli APC in colon cancer, retinoblastoma RB. and von Hippel–Lindau tumor suppressor VHL, as well as a number of proto-oncogenes. The UPS is also involved in the regulation of the inflammatory response. This activity is usually attributed to the role of the proteasome in the activation of NF-KB, which regulates the expression of proinflammatory cytokines such as TNF-α, Il-β, IL-8, adhesion molecules and prostaglandins and of nitric oxide NO. In addition, the UPS also plays a role in inflammatory reactions as a regulator of proliferation of leukocytes, mainly due to proteolytic degradation of cyclines and CDK inhibitors. Finally, autoimmune diseases in patients with SLE, Sjogrens syndrome and rheumatoid arthritis RA predominantly exhibit circulating proteasomes, which can be applied as a clinical biomarker.

In the processing of antigen for major histocompatibility complex class-I MHC, proteasome is the main degradation machinery, which degrades the antigen and present the peptides on cytotoxic T-lymphocytes. In immunoproteasome is considered to play an important role in improving the quality and quantity of the generated class-I ligands.

                                     
  • conjugated linoleic acid CLA in mammary tissue. PSMD 13 has been shown to interact with PSMC4 and PSMD6 GRCh38: Ensembl release 89: ENSG00000185627 - Ensembl
  • nomenclature is an enzyme that in humans is encoded by the PSMD 2 gene. The gene PSMD 2 encodes a non - ATPase subunit of the 19S regulator base, which
  • non - ATPase regulatory subunit 3 is an enzyme that in humans is encoded by the PSMD 3 gene. The 26S proteasome is a multicatalytic proteinase complex with a highly
  • non - ATPase regulatory subunit 8 is an enzyme that in humans is encoded by the PSMD 8 gene. The 26S proteasome is a multicatalytic proteinase complex with a highly
  • non - ATPase regulatory subunit 9 is an enzyme that in humans is encoded by the PSMD 9 gene. The 26S proteasome is a multicatalytic proteinase complex with a highly
  • non - ATPase regulatory subunit 12 is an enzyme that in humans is encoded by the PSMD 12 gene. The 26S proteasome is a multicatalytic proteinase complex with a
  • the PSMD 14 gene. This protein is one of the 19 essential subunits of the complete assembled 19S proteasome complex. Nine subunits Rpn3, Rpn5, Rpn 6 Rpn7
  • non - ATPase regulatory subunit 5 is an enzyme that in humans is encoded by the PSMD 5 gene. The 26S proteasome is a multicatalytic proteinase complex with a highly
  • non - ATPase regulatory subunit 11 is an enzyme that in humans is encoded by the PSMD 11 gene. The 26S proteasome is a multicatalytic proteinase complex with a
  • the PSMD 4 gene. This protein is one of the 19 essential subunits that contributes to the complete assembly of 19S proteasome complex. The gene PSMD 4 encodes