Biological activities of HAP46/BAG-1. The HAP46/BAG-1 protein: regulator of HSP70 chaperones, DNA-binding protein and stimulator of transcription.
HAP46/BAG-1M and its isoforms affect the protein-folding activities of mammalian HSP70 chaperones. They interact with the ATP-binding domain of HSP70 or HSC70, leaving the substrate-binding site available for further interactions. Trimeric complexes can therefore form with, for example, transcription factors. Moreover, HAP46/BAG-1M and the larger isoform HAP50/BAG-1L bind to DNA non-specifically and enhance transcription in vitro and upon overexpression in intact cells. These factors are linked to positive effects on cell proliferation and survival. This review focuses on DNA-binding activity and transcriptional stimulation by HAP46/BAG-1M, and presents a molecular model for the underlying mechanism. It is proposed that transcription factors are recruited into complexes with HAP46/BAG-1M or HAP50/BAG-1L through HSP70/HSC70 and that response-element-bound complexes that contain HAP46/BAG-1M and/or HAP50/BAG-1L along with HSP70s target and affect the basal transcription machinery.
Gehring
Ulrich
U
Universität Heidelberg, c/o Molekulare Evolution und Genomik, Im Neuenheimer Feld 230, D-69120 Heidelberg, Germany. ru-gehring@t-online.de
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism; D017510:Protein Folding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011987:Receptors, Steroid / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D025801:Ubiquitin / Q000737:chemistry / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
C091732:BCL2-associated athanogene 1 protein; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D020033:Protein Isoforms; D011987:Receptors, Steroid; D014157:Transcription Factors; D025801:Ubiquitin