Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, we demonstrated that the antiapoptotic function of Bcl-2 in mast cells is significantly dependent on its association with the heat shock protein 90beta (Hsp90beta). Dissociation of these 2 proteins inhibits the antiapoptotic activity of Bcl-2 by initiating the release of cytochrome c from mitochondria into cytosol and increasing the activity of caspase 3 and caspase 7, resulting in mast-cell apoptosis. The antiapoptotic activity of Bcl-2 was greatly affected by knocking-out specifically Hsp90beta using the RNA interference approach. Thus, for the first time, it has been shown that Hsp90beta might modulate the antiapoptotic activity of Bcl-2 at least in mast cells. These findings could have implications for a novel strategy of regulating apoptosis in patients with mastocytosis and other mast cell-associated diseases.
 ...
PMID:Antiapoptotic function of Bcl-2 in mast cells is dependent on its association with heat shock protein 90beta. 1616 81

Apoptosis or programmed cell death plays an important role in a wide variety of physiological processes. Apoptosis is regulated by proteins of the Bcl-2 family consisting of both anti-apoptotic and pro-apoptotic factors. The direct involvement of the Bcl-2 protein family in the process of mast cell apoptosis has not been clarified. We have used a single-chain antibody (scFv) raised against Bcl-2 derived from human phage-display antibody library. The addition of TAT sequence, which is responsible for translocation through the membrane, endows the anti-Bcl-2-scFv with the ability to penetrate living cells. The association of anti-Bcl-2-scFv-TAT with intracellular Bcl-2 leads to neutralization of Bcl-2 and eradication of its anti-apoptotic activity in two types of mast cells and in a human breast cancer cell line. Moreover, we found by mass spectrometry and co-immunoprecipitation assay that heat shock protein 90b (Hsp90b) forms a complex with Bcl-2 in mast cells. Thus, understanding the network of interactions between Bcl-2 and non-Bcl-2 family members might help in development of more specific drugs and cancer therapy.
 ...
PMID:The involvement of Bcl-2 in mast cell apoptosis. 1660 36

Lichen planus is a chronic mucocutaneous inflammatory disease, which frequently affects the oral mucosa of white females over 40 years old. Its aetiology remains uncertain and the pathogenesis is still the object of much speculation. The present paper presents the most well known antigens, and describes the action of different cells and proteins associated with the development of that disease, as well as the possible agents involved with its malignant transformation. Different external agents, especially virus, and internal agents, like stress, and the heat shock protein antigen expression, associated or not, can alter the basal keratinocytes of the oral mucosa making them susceptible to apoptosis by CD8(+) cytotoxic T cell as well as activate matrix metalloproteinase and mast cell degranulation, which produce a great range of inflammatory mediators and cytokines determining the clinical onset of the disease. Regarding carcinogenesis, since it is a complex process and presents multifactorial origin, it is believed that there may be a synergism between intrinsic, such as inflammation mediators, and extrinsic agents (tobacco, alcohol, viral infections) for the OLP malignant transformation to occur. However, further studies are needed to better understand the origin, pathogenesis and process of malignant transformation of OLP.
...
PMID:Oral lichen planus: focus on etiopathogenesis. 2366 Jan 24

Literature data indicate heat shock protein (Hsp) 32 and 90 as potential molecular targets in canine neoplastic mast cells (MCs). However, their immunoexpression patterns in canine mast cell tumors (MCTs) have not been investigated. Thus, the aim of this study was to evaluate the immunohistochemical expression of Hsp32 and Hsp90 in 22 canine cutaneous MCTs, in relation to KIT immunolabeling pattern, histological grade, and mitotic count. All cases showed cytoplasmic labeling of Hsp90, variably associated with nuclear and/or membranous labeling. Relationships of Hsp90 or Hsp32 immunolabeling with KIT pattern, mitotic count, and tumor grade were not observed. However, the reduced Hsp32 immunoexpression observed in most grade III/high-grade MCTs suggests a tendency toward a loss of immunosignal in poorly differentiated MCs. The great heterogeneity in extent and distribution of Hsp90 immunoexpression among the different MCT cases may also partially explain the difficulties in predicting the in vivo biologic activity of Hsp90 inhibitors on canine MCTs.
 ...
PMID:HSP32 and HSP90 Immunoexpression, in Relation to Kit Pattern, Grading, and Mitotic Count in Canine Cutaneous Mast Cell Tumors. 2762 84