Single-point mutation in a conserved TPR domain of Hip disrupts enhancement of glucocorticoid receptor signaling.
The Hsp70-interacting protein Hip has been identified as a transient participant in the assembly of both glucocorticoid (GR) and progesterone receptor complexes. Although it has been difficult to identify a physiological role for Hip, it is believed to have intrinsic chaperoning properties and has been identified as a potential anti-apoptotic target of Granzyme B. In vitro assays have provided evidence that Hip may interact with GR complexes in an Hsp70 independent manner and can enhance the function of GR in hormone based reporter assays. In this study, a cDNA for human Hip was used in mutational analysis to map Hip function to critical structural elements. A single amino acid substitution (L211S) resulted in a loss of Hip function. This mutation also appears to disrupt the interaction of Hip with Hsp70 in vitro. Failure to recover Hip-L211S constructs in co-immunoprecipitation assays with an Hsp70 monoclonal antibody suggests that the mutation is unlikely to result in a misfolded substrate.
Department of Biological Sciences, University of South Carolina, Columbia, USA. places@mailbox.sc.edu
Sean P
SP
Place
D004252:DNA Mutational Analysis; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation / Q000235:genetics; D017434:Protein Structure, Tertiary; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D018840:HSP70 Heat-Shock Proteins; C105426:Hip chaperone; D018832:Molecular Chaperones; D011965:Receptors, Glucocorticoid
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