Multiple, but concerted cellular activities of the human protein Hap46/BAG-1M and isoforms.

The closely related human and murine proteins Hap46/BAG-1M and BAG-1, respectively, were discovered more than a decade ago by molecular cloning techniques. These and the larger isoform Hap50/BAG-1L, as well as shorter isoforms, have the ability to interact with a seemingly unlimited array of proteins of completely unrelated structures. This problem was partially resolved when it was realized that molecular chaperones of the hsp70 heat shock protein family are major primary association partners, binding being mediated by the carboxy terminal BAG-domain and the ATP-binding domain of hsp70 chaperones.

Activities of the cochaperones Hap46/BAG-1M and Hap50/BAG-1L and isoforms.

Since their discovery about a decade ago, human Hap46/BAG-1M, the larger isoform Hap50/BAG-1L, and related structures have caused quite some astonishment because of the seemingly unlimited array of possible interaction partners belonging to completely unrelated protein families. This problem was partially resolved when it was realized that molecular chaperones of the heat shock protein family Hsp70 are major primary association partners, which in turn, are able to bind a wide variety of unrelated protein structures, thus forming ternary complexes. Moreover, the protein folding activity of Hsp70 chaperones is affected; hence, the designation "cochaperones.

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.

[Glucocorticoid receptors: basis for the diverse clinical actions of glucocorticoids].

Domain structure of the receptor polypeptide and association with accessory proteins: This review summarizes our present knowledge on the different forms of the glucocorticoid receptor emphasizing structure and functional significance. The nonactivated receptor resides in the cytoplasm. It contains the human receptor polypeptide of 777 amino acids as heteromeric complex in association with two molecules of the heat-shock protein hsp90 and one immunophilin.

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.

Transcriptional stimulation by the DNA binding protein Hap46/BAG-1M involves hsp70/hsc70 molecular chaperones.

The hsp70/hsc70-associating protein Hap46 of human origin, also called BAG-1M (Bcl-2-associated athanogene 1), has been characterized previously as a DNA binding protein, which is able to stimulate transcription. By use of in vitro assays we now show that Hap46-mediated transcriptional activation can occur from linearized as well as from supercoiled circular DNA and does not require the presence of a transcription promoter. Accordingly, we observed no preferential binding of Hap46 to overlapping DNA fragments covering the sequence of the cytomegalovirus (CMV) early promoter, thus suggesting non-specific binding.