更新于：2024-05-01
BAG6
BAG cochaperone 6
更新于：2024-05-01
基本信息
别名 BAG cochaperone 6、BAG family molecular chaperone regulator 6、BAG-6 + [10] |
简介 ATP-independent molecular chaperone preventing the aggregation of misfolded and hydrophobic patches-containing proteins (PubMed:21636303). Functions as part of a cytosolic protein quality control complex, the BAG6/BAT3 complex, which maintains these client proteins in a soluble state and participates in their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation (PubMed:20516149, PubMed:21636303, PubMed:21743475, PubMed:28104892). The BAG6/BAT3 complex is involved in the post-translational delivery of tail-anchored/type II transmembrane proteins to the endoplasmic reticulum membrane. Recruited to ribosomes, it interacts with the transmembrane region of newly synthesized tail-anchored proteins and together with SGTA and ASNA1 mediates their delivery to the endoplasmic reticulum (PubMed:20516149, PubMed:20676083, PubMed:28104892, PubMed:25535373). Client proteins that cannot be properly delivered to the endoplasmic reticulum are ubiquitinated by RNF126, an E3 ubiquitin-protein ligase associated with BAG6 and are sorted to the proteasome (PubMed:24981174, PubMed:28104892, PubMed:27193484). SGTA which prevents the recruitment of RNF126 to BAG6 may negatively regulate the ubiquitination and the proteasomal degradation of client proteins (PubMed:23129660, PubMed:25179605, PubMed:27193484). Similarly, the BAG6/BAT3 complex also functions as a sorting platform for proteins of the secretory pathway that are mislocalized to the cytosol either delivering them to the proteasome for degradation or to the endoplasmic reticulum (PubMed:21743475). The BAG6/BAT3 complex also plays a role in the endoplasmic reticulum-associated degradation (ERAD), a quality control mechanism that eliminates unwanted proteins of the endoplasmic reticulum through their retrotranslocation to the cytosol and their targeting to the proteasome. It maintains these retrotranslocated proteins in an unfolded yet soluble state condition in the cytosol to ensure their proper delivery to the proteasome (PubMed:21636303). BAG6 is also required for selective ubiquitin-mediated degradation of defective nascent chain polypeptides by the proteasome. In this context, it may participate in the production of antigenic peptides and play a role in antigen presentation in immune response (By similarity). BAG6 is also involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation. BAG6 may ensure the proper degradation of these proteins and thereby protects the endoplasmic reticulum from protein overload upon stress (PubMed:26565908). By inhibiting the polyubiquitination and subsequent proteasomal degradation of HSPA2 it may also play a role in the assembly of the synaptonemal complex during spermatogenesis (By similarity). Also positively regulates apoptosis by interacting with and stabilizing the proapoptotic factor AIFM1 (By similarity). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333).
Mediates ricin-induced apoptosis.
Involved in DNA damage-induced apoptosis: following DNA damage, accumulates in the nucleus and forms a complex with p300/EP300, enhancing p300/EP300-mediated p53/TP53 acetylation leading to increase p53/TP53 transcriptional activity (PubMed:17403783). When nuclear, may also act as a component of some chromatin regulator complex that regulates histone 3 'Lys-4' dimethylation (H3K4me2) (PubMed:18765639).
Released extracellularly via exosomes, it is a ligand of the natural killer/NK cells receptor NCR3 and stimulates NK cells cytotoxicity. It may thereby trigger NK cells cytotoxicity against neighboring tumor cells and immature myeloid dendritic cells (DC). |
关联
100 项与 BAG6 相关的临床结果
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100 项与 BAG6 相关的转化医学
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2024-01-26Journal of ophthalmic inflammation and infection
In vivo confocal microscopy evaluation of infiltrated immune cells in corneal stroma treated with cell therapy in advanced keratoconus.
Article
作者: Mona El Zarif ; Karim Abdul Jawad ; Jorge L Alió ; Nehman Makdissy ; María P De Miguel
PURPOSE:
This study investigates immune cell (ICs) infiltration in advanced keratoconus patients undergoing autologous adipose-derived adult stem cell (ADASC) therapy with recellularized human donor corneal laminas (CL).
METHODS:
A prospective clinical trial included fourteen patients divided into three groups: G-1, ADASCs; G-2, decellularized CL (dCL); and G-3, dCL recellularized with ADASCs (ADASCs-rCL). Infiltrated ICs were assessed using in vivo confocal microscopy (IVCM) at 1,3,6, and12 months post-transplant.
RESULTS:
Infiltrated ICs, encompassing granulocytes and agranulocytes, were observed across all groups, categorized by luminosity, structure, and area. Stromal ICs infiltration ranged from 1.19% to 6.62%, with a consistent increase in group-related cell density (F = 10.68, P < .0001), independent of post-op time (F = 0.77, P = 0.511); the most substantial variations were observed in G-3 at 6 and 12 months (2.0 and 1.87-fold, respectively). Similarly, significant size increases were more group-dependent (F = 5.76, P < .005) rather than time-dependent (F = 2.84, P < .05); G-3 exhibited significant increases at 6 and 12 months (3.70-fold and 2.52-fold, respectively). A lamina-induced shift in IC size occurred (F = 110.23, P < .0001), primarily with 50-100 μm2 sizes and up to larger cells > 300μm2, presumably macrophages, notably in G-3, indicating a potential role in tissue repair and remodeling, explaining reductions in cells remnants < 50μm2.
CONCLUSIONS:
ADASCs-rCL therapy may lead to increased IC infiltration compared to ADASCs alone, impacting cell distribution and size due to the presence of the lamina. The findings reveal intricate immune patterns shaped by the corneal microenvironment and highlight the importance of understanding immune responses for the development of future therapeutic strategies.
2024-01-15Cancers
Translation into Clinical Practice of the G1-G7 Molecular Subgroup Classification of Glioblastoma: Comprehensive Demographic and Molecular Pathway Profiling.
Article
作者: Maria-Magdalena Georgescu
Glioblastoma is the most frequent and malignant primary neoplasm of the central nervous system. In a recent breakthrough study on a prospective Discovery cohort, I proposed the first all-inclusive molecular classification of glioblastoma into seven subgroups, G1-G7, based on MAPK pathway activation. New data from a WHO-grade-4 diffuse glioma prospective Validation cohort offers, in this study, an integrated demographic-molecular analysis of a 213-patient Combined cohort. Despite cohort differences in the median age and molecular subgroup distribution, all the prospectively-acquired cases from the Validation cohort mapped into one of the G1-G7 subgroups defined in the Discovery cohort. A younger age of onset, higher tumor mutation burden and expanded G1/EGFR-mutant and G3/NF1 glioblastoma subgroups characterized the glioblastomas from African American/Black relative to Caucasian/White patients. The three largest molecular subgroups were G1/EGFR, G3/NF1 and G7/Other. The fourth largest subgroup, G6/Multi-RTK, was detailed by describing a novel gene fusion ST7-MET, rare PTPRZ1-MET, LMNA-NTRK1 and GOPC-ROS1 fusions and their overexpression mechanisms in glioblastoma. The correlations between the MAPK pathway G1-G7 subgroups and the PI3-kinase/PTEN, TERT, cell cycle G1 phase and p53 pathways defined characteristic subgroup pathway profiles amenable to personalized targeted therapy. This analysis validated the first all-inclusive molecular classification of glioblastoma, showed significant demographic and molecular differences between subgroups, and provided the first ethnic molecular comparison of glioblastoma.
2023-12-22Nutrients
Impact of Maternal Mediterranean-Type Diet Adherence on Microbiota Composition and Epigenetic Programming of Offspring.
Article
作者: Tamlyn Sasaki ; Megan Kawamura ; Chirstyn Okuno ; Kayleen Lau ; Jonathan Riel ; Men-Jean Lee ; Corrie Miller
Understanding how maternal diet affects in utero neonatal gut microbiota and epigenetic regulation may provide insight into disease origins and long-term health. The impact of Mediterranean diet pattern adherence (MDA) on fetal gut microbiome and epigenetic regulation was assessed in 33 pregnant women. Participants completed a validated food frequency questionnaire in each trimester of pregnancy; the alternate Mediterranean diet (aMED) score was applied. Umbilical cord blood, placental tissue, and neonatal meconium were collected from offspring. DNA methylation patterns were probed using the Illumnia EPICarray Methylation Chip in parturients with high versus low MDA. Meconium microbial abundance in the first 24 h after birth was identified using 16s rRNA sequencing and compared among neonates born to mothers with high and low aMED scores. Twenty-one mothers were classified as low MDA and 12 as high MDA. Pasteurellaceae and Bacteroidaceae trended towards greater abundance in the high-MDA group, as well as other short-chain fatty acid-producing species. Several differentially methylated regions varied between groups and overlapped gene regions including NCK2, SNED1, MTERF4, TNXB, HLA-DPB, BAG6, and LMO3. We identified a beneficial effect of adherence to a Mediterranean diet on fetal in utero development. This highlights the importance of dietary counseling for mothers and can be used as a guide for future studies of meconium and immuno-epigenetic modulation.
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