Caveolin1 Expression Confers a New Level of Regulation

Caveolin-1 association with a number of proteins can be inhibitory. Likewise, caveolin expression in tissues in which its expression is normally low results in the formation of caveolae. The presence of caveolin then causes docking of signaling proteins, inhibition where proteins were previously constitutively active, and induction of regulatory pathways where they were absent, as a result. For example, expression of caveolin in hepatocytes causes down-regulation of lipid uptake in the liver [35], a tissue that is normally active in the uptake of high-density lipoprotein (HDL), leading to higher circulating levels of lipoproteins as a result. Loss of cav-eolin in cancer removes a regulatory structure, and the inhibitory activity that caveolin-1 confers to a number of signaling proteins, resulting in overactivation of growth signaling. Dysregulation of caveolin-1 is associated with an overactivation of growth signals in breast [36,37], and prostate cancers [38-40]. Several of the growth-signaling pathways which are constitutively turned on in prostate cancer, are found to be associated, and regulated, within caveolae in normal cells. A number of other proteins have also been suggested to be inhibited by the direct binding of caveolin-1.

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