Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the rabbit, a p59 protein included in the untransformed, non-DNA binding, "8-9S," steroid receptor complexes binds heat shock protein M(r) approximately 90,000 (hsp90). Sequence data [Lebeau, M. C., Massol, N., Herrick, J., Faber, L. E., Renoir, J. M., Radanyi, C. & Baulieu, E. E. (1992) J. Biol. Chem. 267, 4281-4284] and hydrophobic cluster analysis delineate, from the N terminus, two successive domains closely related to the immunosuppressant FK506 binding immunophilin FKBP (FK506 binding protein), consistent with recent purification of the human p56 immunophilin cognate protein by FK506 affinity chromatography [Yem, A. W., Tomasselli, A. G., Heinrikson, R. L., Zurcher-Neely, H., Ruff, V. A., Johnson, R. A. & Deibel, M. R., Jr. (1992) J. Biol. Chem. 267, 2868-2871]. The first FKBP-like domain demonstrates all structural characteristics known to be necessary for immunosuppressant binding and for peptidylprolyl cis-trans isomerase (rotamase) activity. Hence, p59 is a "hsp binding immunophilin" (HBI). It is thus speculated that hsp binding immunophilin may help the assembly/disassembly mechanisms involved in steroid receptor trafficking and activity and participate in the poorly understood hsp90 function. ATP/GTP binding likely occurs within the second FKBP-like domain, near the FK506 binding site on the FKBP template. A third domain detected by the hydrophobic cluster analysis method is distantly structurally related to the two first FKBP-like domains and is followed by the C-terminal part of the protein, which contains a calmodulin binding consensus sequence. Hsp binding immunophilin may be involved in a number of immunological, endocrinological, and chaperone-mediated pathways.
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PMID:An immunophilin that binds M(r) 90,000 heat shock protein: main structural features of a mammalian p59 protein. 163 Nov 18

Inflammation may play an important role in the pathophysiology of sickle cell disease (SCD), and recent studies have identified the 70-kDa heat shock protein (Hsp70) as an important mediator of inflammatory responses. Here we demonstrate a significant increase in circulating serum Hsp70 level in SCD during vaso-occlusive crisis (VOC) as compared with baseline steady-state levels (P <0.05) and a significant increase in Hsp70 levels in SCD at baseline compared with normal controls (P <0.05). Taken together, these results indicate that circulating serum Hsp70 might be a marker for VOC in SCD.
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PMID:Sickle cell vaso-occlusive crisis induces the release of circulating serum heat shock protein-70. 1572 96