Translational Regulation of Milk Protein Synthesis at Secretory Activation

Abstract

Studies conducted since the 1970s have revealed that the production of milk proteins in the mammary gland under the influence of lactogenic hormones (insulin, prolactin, and glucocorticoids) is regulated at multiple levels. Whereas earlier studies concentrated on transcriptional regulation and stabilization of milk protein mRNAs, more recent studies have revealed that translation of milk protein mRNAs is also dependent on lactogenic hormones. A general stimulation of translation in mammary epithelial cells is caused by amino acids (as signaling molecules) or by phosphorylation of the translational regulator 4E-BP1 in a synergistic response to signals from insulin and prolactin. However, a selective enhancement of milk protein mRNA translation is caused by cytoplasmic polyadenylation of mRNA, again in a synergistic response to these two hormones. Preliminary evidence indicates that the latter effect depends on the existence of a cytoplasmic polyadenylation element (CPE) in milk protein mRNAs and phosphorylation of its binding protein, CPEB. Experiments in whole animals, organ explants, and cell culture have shown that the poly(A) length of milk protein mRNAs changes as a function of the lactation cycle. Interestingly, cytoplasmic polyadenylation is likely to be responsible for the selective hormone-dependent enhancement of both translation and stability of milk protein mRNAs.