Expression of p27Kip1, A Cell Cycle Repressor Protein with Dual Roles for Both Cancer Prevention and Promotion, Is Regulated Primarily at the Level of Unusual p27Kip1 mRNA—A Short Concept Proposal

摘要

The p27Kip1 is a cell cycle repressor protein that regulatesprimarily the cell cycle transition from G1 to S phase and hence the DNAreplication is in the S phase and cell division in the M phase. Expression of p27Kip1protein has dual roles for both cancer prevention and promotion. For example, numerousnutritional and chemopreventive anti-cancer agents specifically increase theexpression of p27Kip1 protein without directly affecting the expression of anyother cell cycle regulatory proteins. On the other hand, pro-cancer agents(like glucose, insulin and other growth factors frequently seen in obesityand/or diabetes) specifically decrease the expression of p27Kip1 proteinwithout directly affecting the expression of any other cell cycle regulatoryproteins. Unlike expression of any other cell cycle regulatory proteins, expressionof p27Kip1 protein is very unusual. The mRNA of p27Kip1 has a very long andunusual 5’-untranslated region (from -575 to -1 in human). It appears that the5’-untranslated region of p27Kip1 mRNA forms two alternative secondary structures. One increases the expression of p27Kip1 protein when anti-cancer agentsare added and another decrease the expression of p27K1p1 when pro-cancer agentsare added. For this short concept proposal, Dr. Albert Einstein’s “visualizedthought experiments (German: Gedanken experiment)” were used as a fundamentaltool for understanding how either anti- or pro-cancer agents bring the primarystructure of the 5’-untranslated region of p27Kip1 mRNA into two alternativesecondary structures, thereby either increasing or decreasing, respectively, thetranslation initiation of p27Kip1 protein.