Ketosteroid isomerase structure

Elevated serum GPI levels have been used as a prognostic biomarker for colorectal , breast , lung , kidney , gastrointestinal , and other cancers . [8] [14] As AMF, GPI is attributed with regulating cell migration during invasion and metastasis . [8] One study showed that the external layers of breast tumor spheroids (BTS) secrete GPI, which induces epithelial–mesenchymal transition (EMT), invasion, and metastasis in BTS. The GPI inhibitors ERI4P and 6PG were found to block metastasis of BTS but not BTS glycolysis or fibroblast viability. In addition, GPI is secreted exclusively by tumor cells and not normal cells. For these reasons, GPI inhibitors may be a safer, more targeted approach for anti-cancer therapy. [29] GPI also participates in a positive feedback loop with HER2 , a major breast cancer therapeutic target, as GPI enhances HER2 expression and HER2 overexpression enhances GPI expression, and so on. As a result, GPI activity likely confers resistance in breast cancer cells against HER2-based therapies using Herceptin /Trastuzumab, and should be considered as an additional target when treating patients. [24]

The TSH receptor is formed as one polypeptide chain and inserted into the thyroid cell plasma membrane. It undergoes a processing that is reminiscent of that occurring with insulin. A segment of 30 or more amino acids is cut out of the receptor at approximately residue 320, forming a two peptide structure with the chains held together by disulfide bonds. It is thought that both the intact and the processed receptor are functional. The processing of the receptor is thought to involve a matrix metalloprotease-like enzyme cleaving the 120 kDa precursor to form the heterodimeric receptor. Subsequently, reduction of the disulfide bonds by a protein disulfide isomerase may separate the two molecules and lead to shedding of the “alpha” subunit. It is an interesting concept that shedding of the alpha subunit might be intimately related to onset of autoimmunity against the TSH receptor. Shedding of the receptor is augmented by TSH stimulation of thyroid cells (58). The amino-terminal ectodomain of the human TSH receptor has been expressed on the surface of CHO cells as a glycosylphosphatidylinositol-anchored molecule. This material can be released from the cells and is biologically active in that it binds immunoglobulins from serum of patients with Graves’ disease, and displays saturable binding of TSH (46), indicating that all of the “immunologic information” related to production of antibodies resides in the extracellular portion of TSH-R.

Ketosteroid isomerase structure

ketosteroid isomerase structure

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ketosteroid isomerase structureketosteroid isomerase structureketosteroid isomerase structureketosteroid isomerase structureketosteroid isomerase structure