Genomes and Genes
Gene Symbol: Bag-1
Description: BCL2 associated athanogene 1
Alias: BAG-1, HAP, RAP46, BAG family molecular chaperone regulator 1, BCL2-associated athanogene, Bcl-2 associating athanogene-1 protein, Bcl-2-binding protein, glucocortoid receptor-associated protein RAP46, receptor-associated protein, 46-KD
- Elliott E, Tsvetkov P, Ginzburg I. BAG-1 associates with Hsc70.Tau complex and regulates the proteasomal degradation of Tau protein. J Biol Chem. 2007;282:37276-84 pubmed..This data suggests a molecular mechanism through which Tau protein levels are regulated in the cell and possible consequences for the pathology and treatment of Alzheimer disease. ..
- Lee S, Crabb S, Janghra N, Carlberg C, Williams A, Cutress R, et al. Subcellular localisation of BAG-1 and its regulation of vitamin D receptor-mediated transactivation and involucrin expression in oral keratinocytes: implications for oral carcinogenesis. Exp Cell Res. 2007;313:3222-38 pubmed..By contrast to the cytoplasmic BAG-1 isoforms, BAG-1L may act to suppress tumorigenesis. ..
- Knee D, Froesch B, Nuber U, Takayama S, Reed J. Structure-function analysis of Bag1 proteins. Effects on androgen receptor transcriptional activity. J Biol Chem. 2001;276:12718-24 pubmed..Four isoforms of Bag1 have been recognized: Bag1, Bag1S, Bag1M (RAP46/HAP46), and Bag1L...
- Sondermann H, Scheufler C, Schneider C, Hohfeld J, Hartl F, Moarefi I. Structure of a Bag/Hsc70 complex: convergent functional evolution of Hsp70 nucleotide exchange factors. Science. 2001;291:1553-7 pubmed..Thus, functional convergence has allowed proteins with different architectures to trigger a conserved conformational shift in Hsp70 that leads to nucleotide exchange. ..
- Takahashi N, Sasaki R, Takahashi J, Takayama S, Reed J, Andoh T. BAG-1M, an isoform of Bcl-2-interacting protein BAG-1, enhances gene expression driven by CMV promoter. Biochem Biophys Res Commun. 2001;286:807-14 pubmed..Our study demonstrates that both N-terminal DNA binding site and C-terminal Hsp70/Hsc70 binding site of BAG-1M play an important role in enhancing the CMV promoter activity. ..
- Demand J, Alberti S, Patterson C, Hohfeld J. Cooperation of a ubiquitin domain protein and an E3 ubiquitin ligase during chaperone/proteasome coupling. Curr Biol. 2001;11:1569-77 pubmed..The chaperone cofactors thus act as key regulators to influence protein quality control. ..
- Alberti S, Demand J, Esser C, Emmerich N, Schild H, Hohfeld J. Ubiquitylation of BAG-1 suggests a novel regulatory mechanism during the sorting of chaperone substrates to the proteasome. J Biol Chem. 2002;277:45920-7 pubmed..Our data thus reveal a cooperative recognition of sorting signals at the proteolytic complex. Attachment of polyubiquitin chains to delivery factors may represent a novel mechanism to regulate protein sorting to the proteasome. ..
- Hung W, Roberson R, Taft J, Wu D. Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions. Mol Cell Biol. 2003;23:3477-86 pubmed..Our findings suggest that BAG-1 may function to suppress the GADD34-mediated cellular stress response and support a role for BAG-1 in the survival of cells undergoing stress. ..
- Arndt V, Daniel C, Nastainczyk W, Alberti S, Hohfeld J. BAG-2 acts as an inhibitor of the chaperone-associated ubiquitin ligase CHIP. Mol Biol Cell. 2005;16:5891-900 pubmed..The presented data therefore establish multiple mechanisms to control the destructive activity of the CHIP ubiquitin ligase in human cells. ..
- Barnes J, Arhel N, Lee S, Sharp A, Al Okail M, Packham G, et al. Nuclear BAG-1 expression inhibits apoptosis in colorectal adenoma-derived epithelial cells. Apoptosis. 2005;10:301-11 pubmed..This demonstrates that nuclear localisation of the BAG-1 protein confers a survival advantage in colorectal adenoma-derived cells and that nuclear BAG-1 could potentially be an important survival factor in colorectal carcinogenesis. ..
- Liman J, Ganesan S, Dohm C, Krajewski S, Reed J, Bahr M, et al. Interaction of BAG1 and Hsp70 mediates neuroprotectivity and increases chaperone activity. Mol Cell Biol. 2005;25:3715-25 pubmed..Together, these results suggest that BAG1-induced activation of Hsp70 is important for neuroprotectivity, while BAG1-dependent modulation of neuronal differentiation in vitro is not. ..
- Clemo N, Collard T, Southern S, Edwards K, Moorghen M, Packham G, et al. BAG-1 is up-regulated in colorectal tumour progression and promotes colorectal tumour cell survival through increased NF-kappaB activity. Carcinogenesis. 2008;29:849-57 pubmed publisher..It is proposed that, by inhibiting NF-kappaB, suppression of BAG-1 could represent a novel strategy to impede colorectal cancer cell survival and as an adjuvant increase sensitivity to current therapeutic regimes. ..
- Lüders J, Demand J, Hohfeld J. The ubiquitin-related BAG-1 provides a link between the molecular chaperones Hsc70/Hsp70 and the proteasome. J Biol Chem. 2000;275:4613-7 pubmed..A regulatory function of the chaperone cofactor at the interface between protein folding and protein degradation is thus indicated. ..
- Gebauer M, Zeiner M, Gehring U. Interference between proteins Hap46 and Hop/p60, which bind to different domains of the molecular chaperone hsp70/hsc70. Mol Cell Biol. 1998;18:6238-44 pubmed..Thus, not only do the major domains of hsp70 chaperones communicate with each other, but cofactors interacting with these domains affect each other as well. ..
- Wang X, O Connor D, Brimmell M, Packham G. The BAG-1 cochaperone is a negative regulator of p73-dependent transcription. Br J Cancer. 2009;100:1347-57 pubmed publisher..Inhibition of p73 function may be one mechanism that contributes to the pro-survival activity of BAG-1. ..
- Kullmann M, Schneikert J, Moll J, Heck S, Zeiner M, Gehring U, et al. RAP46 is a negative regulator of glucocorticoid receptor action and hormone-induced apoptosis. J Biol Chem. 1998;273:14620-5 pubmedb>RAP46 was first identified by its ability to bind the glucocorticoid receptor...
- Matsuzawa S, Takayama S, Froesch B, Zapata J, Reed J. p53-inducible human homologue of Drosophila seven in absentia (Siah) inhibits cell growth: suppression by BAG-1. EMBO J. 1998;17:2736-47 pubmed..We suggest that Siah-1A may be an important mediator of p53-dependent cell-cycle arrest and demonstrate that Siah-1A is directly inhibited by BAG-1. ..
- Hong W, Baniahmad A, Li J, Chang C, Gao W, Liu Y. Bag-1M inhibits the transactivation of the glucocorticoid receptor via recruitment of corepressors. FEBS Lett. 2009;583:2451-6 pubmed publisher..In addition, Bag-1M is not involved in the degradation of the receptor. These findings indicate a novel mechanism by which Bag-1M acts as a corepressor and downregulates the activity of the GR. ..
- Zhang X, Pfeiffer H, Mellert H, Stanek T, Sussman R, Kumari A, et al. Inhibition of the single downstream target BAG1 activates the latent apoptotic potential of MYC. Mol Cell Biol. 2011;31:5037-45 pubmed publisher..Ultimately, the synthetic lethality we have identified between MYC overexpression and BAG1 inhibition establishes a new pathway that might be exploited to reactivate the latent apoptotic potential of MYC as a cancer therapy. ..
- Zeiner M, Gehring U. A protein that interacts with members of the nuclear hormone receptor family: identification and cDNA cloning. Proc Natl Acad Sci U S A. 1995;92:11465-9 pubmed..e., release from heat shock proteins. The sequence identified here appears to be a general partner protein for nuclear hormone receptors, with the gene being expressed in a variety of mammalian tissues. ..
- Hong W, Baniahmad A, Liu Y, Li H. Bag-1M is a component of the in vivo DNA-glucocorticoid receptor complex at hormone-regulated promoter. J Mol Biol. 2008;384:22-30 pubmed publisher..These findings identify a regulatory mechanism, downstream of hormone binding, used by Bag-1M for attenuating GR action in response to its changing cellular levels. ..
- Millar E, Anderson L, McNeil C, O Toole S, Pinese M, Crea P, et al. BAG-1 predicts patient outcome and tamoxifen responsiveness in ER-positive invasive ductal carcinoma of the breast. Br J Cancer. 2009;100:123-33 pubmed publisher..A high BAG-1 expression predicts improved patient outcome in ER+ breast carcinoma. This may reflect both a better definition of the hormone-responsive phenotype and a concurrent increased sensitivity to tamoxifen. ..
- Krajewska M, Turner B, Shabaik A, Krajewski S, Reed J. Expression of BAG-1 protein correlates with aggressive behavior of prostate cancers. Prostate. 2006;66:801-10 pubmed..04) and shorter time to disease progression (P = 0.00004). Increased cytosolic and nuclear BAG-1 expression may denote more aggressive variants of prostate cancer. ..
- Sharp A, Cutress R, Johnson P, Packham G, Townsend P. Short peptides derived from the BAG-1 C-terminus inhibit the interaction between BAG-1 and HSC70 and decrease breast cancer cell growth. FEBS Lett. 2009;583:3405-11 pubmed publisher..In conclusion, we have identified a small domain within BAG-1 which appears to play a critical role in the interaction with HSC70. ..
- Xiong J, Chen J, Chernenko G, Beck J, Liu H, Pater A, et al. Antisense BAG-1 sensitizes HeLa cells to apoptosis by multiple pathways. Biochem Biophys Res Commun. 2003;312:585-91 pubmed
- Packham G, Brimmell M, Cleveland J. Mammalian cells express two differently localized Bag-1 isoforms generated by alternative translation initiation. Biochem J. 1997;328 ( Pt 3):807-13 pubmed..The human Bag-1 cDNA is essentially identical with a previously described cDNA encoding RAP46, which interacts with activated steroid hormone receptors...
- Takayama S, Bimston D, Matsuzawa S, Freeman B, Aime Sempe C, Xie Z, et al. BAG-1 modulates the chaperone activity of Hsp70/Hsc70. EMBO J. 1997;16:4887-96 pubmed..The inhibitory effects of BAG-1 on Hsp/Hsc70 chaperone activity suggest that BAG-1 represents a novel type of chaperone regulatory proteins and thus suggest a link between cell signaling, cell death and the stress response. ..
- Froesch B, Takayama S, Reed J. BAG-1L protein enhances androgen receptor function. J Biol Chem. 1998;273:11660-6 pubmed..BAG-1L, but not BAG-1 or BAG-1M (RAP46), also markedly enhanced the ability of AR to transactivate reporter gene plasmids containing an androgen response ..
- Liu R, Takayama S, Zheng Y, Froesch B, Chen G, Zhang X, et al. Interaction of BAG-1 with retinoic acid receptor and its inhibition of retinoic acid-induced apoptosis in cancer cells. J Biol Chem. 1998;273:16985-92 pubmedBAG-1 (also known as RAP46) is an anti-apoptotic protein, which has been shown previously to interact with a number of nuclear hormone receptors, including receptors for glucocorticoid, estrogen, and thyroid hormone...
- Takayama S, Krajewski S, Krajewska M, Kitada S, Zapata J, Kochel K, et al. Expression and location of Hsp70/Hsc-binding anti-apoptotic protein BAG-1 and its variants in normal tissues and tumor cell lines. Cancer Res. 1998;58:3116-31 pubmed
- Yang X, Chernenko G, Hao Y, Ding Z, Pater M, Pater A, et al. Human BAG-1/RAP46 protein is generated as four isoforms by alternative translation initiation and overexpressed in cancer cells. Oncogene. 1998;17:981-9 pubmed..isolated by us and two other groups, has been shown to be identical to a hormone receptor-binding protein, RAP46. However, different molecular masses of hBAG-1 protein products were noted by these three groups...
- Takayama S, Xie Z, Reed J. An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators. J Biol Chem. 1999;274:781-6 pubmed..The findings suggest opportunities for specification and diversification of Hsp70/Hsc70 chaperone functions through interactions with various BAG-family proteins. ..
- Wang H, Takayama S, Rapp U, Reed J. Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1. Proc Natl Acad Sci U S A. 1996;93:7063-8 pubmed..BAG-1 also activates this mammalian kinase in yeast. These observations suggest that the Bcl-2 binding protein BAG-1 joins Ras and 14-3-3 proteins as potential activators of the kinase Raf-1. ..
- Song J, Takeda M, Morimoto R. Bag1-Hsp70 mediates a physiological stress signalling pathway that regulates Raf-1/ERK and cell growth. Nat Cell Biol. 2001;3:276-82 pubmed..We propose that Bag1 functions in the heat-shock response to coordinate cell growth signals and mitogenesis, and that Hsp70 functions as a sensor in stress signalling. ..
- Takayama S, Sato T, Krajewski S, Kochel K, Irie S, Millan J, et al. Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein with anti-cell death activity. Cell. 1995;80:279-84 pubmed
- Townsend P, Cutress R, Carroll C, Lawrence K, Scarabelli T, Packham G, et al. BAG-1 proteins protect cardiac myocytes from simulated ischemia/reperfusion-induced apoptosis via an alternate mechanism of cell survival independent of the proteasome. J Biol Chem. 2004;279:20723-8 pubmed..Our studies demonstrate that BAG-1 can influence cellular response to stress by multiple mechanisms, potentially influenced by the cell type and nature of the stress signal. ..
- Kikuchi R, Noguchi T, Takeno S, Funada Y, Moriyama H, Uchida Y. Nuclear BAG-1 expression reflects malignant potential in colorectal carcinomas. Br J Cancer. 2002;87:1136-9 pubmed..013). These studies demonstrate that nuclear BAG-1 expression is a useful predictive factor for distant metastasis and a poor prognosis in patients with colorectal cancer. ..
- Arhel N, Packham G, Townsend P, Collard T, H Zadeh A, Sharp A, et al. The retinoblastoma protein interacts with Bag-1 in human colonic adenoma and carcinoma derived cell lines. Int J Cancer. 2003;106:364-71 pubmed..Our work establishes that the Rb protein interacts with the Bag-1 apoptotic regulator protein, and introduces a novel function for Rb, involving modulation of the subcellular localisation of Bag-1 in human colonic epithelial cells. ..
- Yang X, Pater A, Tang S. Cloning and characterization of the human BAG-1 gene promoter: upregulation by tumor-derived p53 mutants. Oncogene. 1999;18:4546-53 pubmed..These results indicated that we have isolated the functional constitutive BAG-1 promoter. Furthermore, the data suggested that overexpression of BAG-1 in some tumors may be due to upregulation of the human BAG-1 promoter by mutant p53. ..
- Liu H, Liang Y, Li Y, Li Y, Wang J, Wu H, et al. Gene silencing of BAG-1 modulates apoptotic genes and sensitizes lung cancer cell lines to cisplatin-induced apoptosis. Cancer Biol Ther. 2010;9:832-40 pubmed..Thus, silencing of the BAG-1 gene resulted in changes in expression of apoptosis-related genes and sensitized A549 and L9981 cells to cisplatin-induced apoptosis. ..
- Mata Greenwood E, Stewart J, Steinhorn R, Pearce W. Role of BCL2-associated athanogene 1 in differential sensitivity of human endothelial cells to glucocorticoids. Arterioscler Thromb Vasc Biol. 2013;33:1046-55 pubmed publisher..In vitro endothelial sensitivity to Dex varies within individuals and is inversely proportional to BAG1 protein expression and glucocorticoid receptor protein turnover. ..
- Lin P, Wu T, Wu D, Wang L, Chen C, Lee H. An increase in BAG-1 by PD-L1 confers resistance to tyrosine kinase inhibitor in non-small cell lung cancer via persistent activation of ERK signalling. Eur J Cancer. 2017;85:95-105 pubmed publisher..We therefore suggest a combination of an ERK inhibitor with a TKI as a potential strategy for conquering PD-L1-mediated tumour invasion and TKI resistance in NSCLC patients whose tumours harbour high PD-L1/high BAG-1 expression. ..
- Wood R, Ormsby A, Radwan M, Cox D, Sharma A, Vöpel T, et al. A biosensor-based framework to measure latent proteostasis capacity. Nat Commun. 2018;9:287 pubmed publisher..This scheme opens new paths for biosensors of disease and proteostasis systems. ..
- Hong W, Chen L, Liu Y, Gao W. ATP hydrolysis is essential for Bag-1M-mediated inhibition of the DNA binding by the glucocorticoid receptor. Biochem Biophys Res Commun. 2009;390:77-81 pubmed publisher..These results indicate that ATP hydrolysis is essential for Bag-1M-mediated inhibition of the DNA binding by the GR and Hsp70 is a mediator for this process. ..
- Deregibus M, Cantaluppi V, Doublier S, Brizzi M, Deambrosis I, Albini A, et al. HIV-1-Tat protein activates phosphatidylinositol 3-kinase/ AKT-dependent survival pathways in Kaposi's sarcoma cells. J Biol Chem. 2002;277:25195-202 pubmed
- Vora H, Mehta S, Shah K, Brahmbhatt B, Desai N, Shukla S, et al. Cytoplasmic localization of BAG-1 in leukoplakia and carcinoma of the tongue: correlation with p53 and c-erbB2 in carcinoma. Int J Biol Markers. 2007;22:100-7 pubmed..The present study evaluated the clinical significance of BAG-1, an antiapoptotic protein, in leukoplakia and carcinoma of the tongue...
- Rizzo M, Berti G, Russo F, Evangelista M, Pellegrini M, Rainaldi G. The miRNA Pull Out Assay as a Method to Validate the miR-28-5p Targets Identified in Other Tumor Contexts in Prostate Cancer. Int J Genomics. 2017;2017:5214806 pubmed publisher..In general terms, these findings support the miRNA pull out assay as a useful method to identify context-specific miRNA targets...
- Gehring U. Activities of the cochaperones Hap46/BAG-1M and Hap50/BAG-1L and isoforms. Cell Stress Chaperones. 2006;11:295-303 pubmed..This is the molecular basis for their effects on transcriptional activities, which are emphasized in this review and for which a molecular model is presented. ..
- Tzankov S, Wong M, Shi K, Nassif C, Young J. Functional divergence between co-chaperones of Hsc70. J Biol Chem. 2008;283:27100-9 pubmed publisher..These results suggest a more complex model of Hsc70 mechanism than has been previously thought, with notable functional divergence between Hsc70 co-chaperones. ..
- Porichi O, Nikolaidou M, Apostolaki A, Arnogiannaki N, Papassideri I, Chatonidis I, et al. Isomorph expression of BAG-1 gene, ER and PR in endometrial cancer. Anticancer Res. 2010;30:4103-8 pubmed..BAG-1 nuclear isomorph appeared more frequently in grade 2 tumors than in grade 1 and 3 tumors, and the cytoplasmatic isomorph was expressed more strongly than the nuclear one. ..
- Bai Y, Yi J, Li J, Sui H. Clinicopathologic significance of BAG1 and TIMP3 expression in colon carcinoma. World J Gastroenterol. 2007;13:3883-5 pubmed..BAG1 and TIMP3 might be new biological parameters in predicting invasion and metastasis of colon carcinoma. ..
- Afentakis M, Dowsett M, Sestak I, Salter J, Howell T, Buzdar A, et al. Immunohistochemical BAG1 expression improves the estimation of residual risk by IHC4 in postmenopausal patients treated with anastrazole or tamoxifen: a TransATAC study. Breast Cancer Res Treat. 2013;140:253-62 pubmed publisher..Similar results were seen if all recurrences were the endpoints. BAG1 expression provides significant prognostic information when added to the classical clinicopathological parameters and IHC4, particularly in node-positive patients. ..
- Sun N, Tian A, Liu Z, Hu S, Hu A. Antiapoptotic gene BAG-1 vector structure of RNA interference and endogenous targeted screening in colon cancer cell lines. Tumour Biol. 2014;35:1057-63 pubmed publisher..It showed the remarkable advantage of RNAi in the generation of posttranscriptional gene silencing. ..
- Knapp R, Wong M, Kollmannsberger L, Gassen N, Kretzschmar A, Zschocke J, et al. Hsp70 cochaperones HspBP1 and BAG-1M differentially regulate steroid hormone receptor function. PLoS ONE. 2014;9:e85415 pubmed publisher..Overall, BAG-1M and HspBP1 had differential impacts on the dynamic composition of steroid receptor folding complexes and on receptor function with important implications for steroid receptor physiology. ..
- Jehle K, Cato L, Neeb A, Muhle Goll C, Jung N, Smith E, et al. Coregulator control of androgen receptor action by a novel nuclear receptor-binding motif. J Biol Chem. 2014;289:8839-51 pubmed publisher..We have therefore identified GARRPR as a novel BF-3 regulatory sequence important for fine-tuning the activity of the AR. ..
- Nugent A, Speicher D, Gradisar I, McBurney D, Baraga A, Doane K, et al. Advanced osteoarthritis in humans is associated with altered collagen VI expression and upregulation of ER-stress markers Grp78 and bag-1. J Histochem Cytochem. 2009;57:923-31 pubmed publisher..These results suggest that chondrocytes exhibit ER stress during OA, in association with upregulation of a large secreted molecule, type VI collagen. ..
- Yoshino K, Motoyama S, Koyota S, Shibuya K, Usami S, Maruyama K, et al. IGFBP3 and BAG1 enhance radiation-induced apoptosis in squamous esophageal cancer cells. Biochem Biophys Res Commun. 2011;404:1070-5 pubmed publisher..IGFBP3 and BAG1 may thus be useful targets for improved and more individualized treatments for patients with esophageal squamous cell carcinoma. ..
- Leznicki P, Roebuck Q, Wunderley L, Clancy A, Krysztofinska E, Isaacson R, et al. The association of BAG6 with SGTA and tail-anchored proteins. PLoS ONE. 2013;8:e59590 pubmed publisher..Such effectors may include SGTA, and the resulting assemblies influence the subsequent fate of the hydrophobic BAG6 substrates. ..
- Ma F, Zhang M, Gong W, Weng M, Quan Z. MiR-138 Suppresses Cell Proliferation by Targeting Bag-1 in Gallbladder Carcinoma. PLoS ONE. 2015;10:e0126499 pubmed publisher..Overexpression of miR-138 inhibited cell proliferation by directly suppressing the expression of Bag-1. These results suggest that miR-138 plays an important role in inhibiting the growth of gallbladder carcinoma. ..