Multiple biological activities of the mammalian protein Hap46/BAG-1.
One of the most prominent features of the mammalian protein Hap46/BAG-1M and its isoforms is the ability to form complexes with an enormous variety of unrelated proteins. In the majority of these interactions, however, molecular chaperones of the hsp70 heat shock protein family are the primary interaction partners which themselves are able to bind very different protein structures by making use of their respective substrate-binding domains. The carboxy terminal portion of Hap46/BAG-1M and its isoforms, called the BAG domain, interacts with the adenosine triphosphate (ATP)-binding domain of hsp70 chaperones and thereby affects their protein folding activities. On the other hand, the amino terminal region of Hap46/BAG-1M, rich in basic amino acid residues, mediates the binding to DNA which, however, has no nucleotide sequence specificity. Hap46/BAG-1M can simultaneously interact with DNA and a chaperone of the hsp70 family. Importantly, Hap46/BAG-1M and the larger isoform Hap50/BAG-1L are able to stimulate transcription in vitro and upon overexpression in intact cells, and both the DNA binding region as well as the BAG domain participate in this effect. A model discusses how such stimulation of transcription may occur molecularly. Increased transcriptional activity in cells expressing high levels of Hap46/BAG-1M and the large isoform Hap50/BAG-1L is related to positive effects on proliferation and survival of such cells. Thus, Hap46/BAG-1M and Hap50/BAG-1L now gain significance as tumor markers.
Gehring
Ulrich
U
Molecular Evolution and Genomics, University of Heidelberg, Heidelberg, Germany. RU-Gehring@T-online.de
D000818:Animals; D014408:Biomarkers, Tumor; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D007536:Isomerism; D008958:Models, Molecular; D011485:Protein Binding; D014157:Transcription Factors
C091732:BCL2-associated athanogene 1 protein; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D014157:Transcription Factors