Cancer-associated SCM-recognition, immunedefense suppression, and serine protease protection peptide. Part III. CRISPP peptide protection of serine proteases against inhibition.
The cancer SCM-recognition, immunedefense suppression, and serine protease protection (CRISPP) peptide, produced by cancer cells, is homologous to the Pn', enzyme-baiting region of the serine protease inhibitor alpha 1-PI. In contrast to the inhibitory function of the intact alpha 1-PI, the CRISPP peptide protects cancer-associated serine proteases against inhibition by alpha 1-PI. In the presence of alpha 1-PI, the prevention of inhibition is a competitive, concentration-dependent process. The shortest fragment of the 29 amino acid sequence of the synthetic, CRISPPs peptide, which protects serine proteases against inhibition as efficiently as the whole molecule, encompasses the amino terminal amino acid residues 1 to 7. Serine proteases and their inhibitor, alpha 1-PI, are involved in the control of many intra- and extracellular physiological processes, including degradative actions in cancer cell invasion, metastatic spread, and neovascularization of tumors. The CRISPP peptide protection of serine proteases against inhibition could unbalance the regulatory controls requiring limited proteolysis by serine proteases. The inherited and/or acquired aberrations resulting in the production of CRISPP peptides in cancer cells could, therefore, be one of the key factors involved in the carcinogenic transformation, enhancing uncontrolled gene derepression and DNA synthesis, and supporting invasion and metastasis. A hypothesis on the mechanism of CRISPP peptide action is proposed.
Cercek
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Beckman Instruments Inc., Diagnostic Systems Group, Brea, CA 92621.
Cercek
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D000939:Epitopes; D006801:Humans; D009363:Neoplasm Proteins / Q000737:chemistry / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000187:drug effects / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000378:metabolism*; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
D000939:Epitopes; D009363:Neoplasm Proteins; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; C079042:cancer-recognition, immunedefense suppression, serine protease protection peptide; D012697:Serine Endopeptidases