Regulation of protein synthesis: translational control by procollagen-derived fragments.

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Abstract
A type I procollagen-derived peptide, called pN.alpha.1(I)-Col 1, selectively inhibits collagen synthesis by fibroblasts in culture and the translation of procollagen mrNA in a rabbit reticulocyte lysate system. The 10,700-dalton peptide from dermatosparactic calf skin, which contained high levels of incompletely processed type I procollagen, was prepared by collagenase digestion. Time-course and dose-response studies showed that the peptide specifically inhibited the translation of procollagen mRNA in preparations of human fibroblast RNA while not affecting the translation of globin mRNA or of other mRNA in fibroblast RNA. After reduction and alkylation, the peptide lost its specificity but became a nonspecific inhibitor of translation. Enzymatic cleavage enabled localization of the nonspecific activity to a short sequence, -Pro-Thr-Asp-Glu and assignment confirmed by peptide synthesis. Using pactamycin, a specific inhibitor of translational initiation, the intact peptide was shown to act on procollagen mRNA translation by inhibition of polypeptide chain elongation and/or termination; the nonspecific inhibitory activity of the unfolded peptide and its derivatives can be attributed to an inhibition of chain initiation. Although the native peptide may function in feedback regulation of collagen synthesis, the physiological role of the lower MW fragments, if any, is uncertain.

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