Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Psoriasis is a T cell-mediated inflammatory disease characterized by hyperproliferation and by aberrant differentiation. We found cathepsin D and zinc-alpha(2)-glycoprotein, two catalytic enzymes associated with apoptosis and desquamation, to be present in the stratum corneum of the normal epidermis but absent from the psoriatic plaque. Psoriasis is characterized by an altered response to interferon-gamma (IFN-gamma), including the induction of apoptosis in normal but not in psoriatic keratinocytes, often with opposite effects on gene expression of suprabasal proteins. We found that IFN-gamma binding and signaling were attenuated in psoriasis: The IFN-gamma receptor, the signal transducer and activator of transcription STAT-1, and the interferon regulatory factor IRF-1 were strongly up-regulated by IFN-gamma in normal keratinocytes, but not in psoriatic ones. IFN-gamma strongly up-regulated the expression of the catalytic enzymes cathepsin D and zinc-alpha(2)-glycoprotein in normal keratinocytes but down-regulated them in psoriatic ones; the reverse was true of the apoptotic suppressor bcl-2. We believe that the aberrant response to IFN-gamma plays a central role in the pathophysiology of psoriasis, particularly the disruption of apoptosis and desquamation.
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PMID:Response of keratinocytes from normal and psoriatic epidermis to interferon-gamma differs in the expression of zinc-alpha(2)-glycoprotein and cathepsin D. 1069 72

S100P is a 95-amino-acid protein and a member of the S100 family. It was first purified from placenta. The promoter area of S100P has binding sites for SMAD, STAT/CREB and SP/KLF, key regulatory elements participating in transcriptional activation of the S100P gene. Increased levels of S100P have been observed in multiple tumor cell lines and breast, pancreas, lung and ovary carcinomas. S100P has been shown to mediate tumor growth, metastasis and invasion through the binding of Ca(2+) ions, receptor for advanced glycation end products, cytoskeletal protein ezrin, calcyclin-binding protein/Siah-1-interacting protein and cathepsin D. S100P could potentially serve as diagnostic marker, prognostic/predictive indicator and therapy target for different carcinomas.
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PMID:Calcium-binding protein S100P and cancer: mechanisms and clinical relevance. 2194 42