Characterization of Hap/BAG‐1 variants as RP1 binding proteins with antiapoptotic activity

Wadle, Andreas; Mischo, Axel; Henrich, Philipp P.; Stenner-Lieven, Frank; Scherer, Christoph; Imig, Jochen; Petersen, Gabriele; Pfreundschuh, Michael; Renner, Christoph

doi:10.1002/ijc.21259

Cited by 7 publications

(2 citation statements)

References 43 publications

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“…Interestingly, a variant of Hap50/BAG-1L has been isolated from a human T-cell cDNA library in a yeast two-hybrid screen. This turned out to be carboxy terminally truncated by 34 amino acids and harbors alterations within terminal residues [ 61 ]; as a consequence, it is unable to interact with hsp70 molecular chaperones. This variant is nevertheless able to associate with the tubulin-associating protein RP1.…”

Section: Interactions With Proteins Independent Of Hsp70 Molecular Chmentioning

confidence: 99%

Multiple, but Concerted Cellular Activities of the Human Protein Hap46/BAG-1M and Isoforms

Gehring

2009

IJMS

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Abstract: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 ATPbinding domain of hsp70 chaperones. The latter, in turn, can associate with an almost unlimited variety of proteins through their substrate-binding domains, so that ternary complexes may result. The protein folding activity of hsp70 chaperones is affected by interactions with Hap46/BAG-1M or isoforms. However, there also exist several proteins which bind to Hap46/BAG-1M and isoforms independent of hsp70 mediation. Moreover, Hap46/BAG-1M and Hap50/BAG-1L, but not the shorter isoforms, can bind to DNA in a sequence-independent manner by making use of positively charged regions close to their amino terminal ends. This is the molecular basis for their effects on transcription which are of major physiological relevance, as discussed here in terms of a model. The related proteins Hap50/BAG-1L and Hap46/BAG-1M may thus serve as molecular links between such diverse bioactivities as regulation of gene expression and protein quality control. These activities are coordinated and synergize in helping cells to cope with conditions of external stress. Moreover, they recently became markers for the aggressiveness of several cancer types. OPEN ACCESS

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Section: Interactions With Proteins Independent Of Hsp70 Molecular Chmentioning

confidence: 99%

Multiple, but Concerted Cellular Activities of the Human Protein Hap46/BAG-1M and Isoforms

Gehring

2009

IJMS

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“…This turned out to be carboxy terminally truncated by 34 amino acids and harbors alterations within the last stretch of residues (Wadle et al 2005); consequently, it is unable to interact with Hsp70 chaperones. Because this variant was able to bind the tubulin-associating protein RP1, RP1 has to be regarded as another direct interaction partner of Hap50/BAG-1L, as well as Hap46/BAG-1M and other isoforms, thus linking these cochaperones to the microtubule system.…”

Section: Binding To Proteins Independent Of Hsp70/hsc70 Chaperonesmentioning

confidence: 99%

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

Gehring

2006

Cell Stress Chaper

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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.'' Although many different proteins require mediation by Hsp70 chaperones for interactions with Hap50/BAG-1L, Hap46/BAG-1M, and isoforms, several other partner proteins are able to associate directly. In addition, Hap46/BAG-1M and Hap50/BAG-1L are also able to interact with DNA by making use of a positively charged region close to the amino terminal end of the polypeptide chain. 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. DISCOVERY OF BAG-1 AND HAP46/BAG-1MRoughly a decade has elapsed since the discovery of the intimately related proteins BAG-1 and Hap46/BAG-1M by molecular cloning techniques. This occurred independently in 3 laboratories that were interested in very different biological processes. Takayama et al (1995) searched for interaction partners for the antiapoptotic protein Bcl-2, and they isolated from a mouse embryonic expression library a cDNA coding for a 219-amino acid sequence. In transfection experiments, the protein exhibited inhibitory effects on apoptosis induced by several stimuli and was therefore termed Bcl-2-associated athanogen-in short, BAG-1-with the Greek word athánatos meaning ''against death.'' The same murine expression library was also used by Bardelli et al (1996), but with the plasma membrane receptor for hepatocyte growth factor as bait protein, leading to the isolation of a series of cDNA clones coding for BAG-1. A third group was interested in binding partners for the activated glucocorticoid receptor (ie, the nuclear form of this intracellular

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Identification and isolation of Dictyostelium microtubule-associated protein interactors by tandem affinity purification

Koch¹,

Reinders²,

Ho³

et al. 2006

European Journal of Cell Biology

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Characterization of Hap/BAG‐1 variants as RP1 binding proteins with antiapoptotic activity

Cited by 7 publications

References 43 publications

Multiple, but Concerted Cellular Activities of the Human Protein Hap46/BAG-1M and Isoforms

Multiple, but Concerted Cellular Activities of the Human Protein Hap46/BAG-1M and Isoforms

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

Identification and isolation of Dictyostelium microtubule-associated protein interactors by tandem affinity purification

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