TITLE:
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
AUTHORS:
Isao Eto
KEYWORDS:
p27Kip1, Cell Cycle Repressor Protein, Cancer Prevention, Anti-Cancer Agents, Cancer Promotion, Pro-Cancer Agents, p27Kip1 mRNA, 5-Prime-Untranslated Region, Translation Initiation, 5-Prime Cap, Upstream Open Reading Frame, Internal Ribosome Entry Site
JOURNAL NAME:
American Journal of Molecular Biology,
Vol.8 No.3,
July
24,
2018
ABSTRACT: The p27Kip1 is a cell cycle repressor protein that regulates
primarily the cell cycle transition from G1 to S phase and hence the DNA
replication is in the S phase and cell division in the M phase. Expression of p27Kip1
protein has dual roles for both cancer prevention and promotion. For example, numerous
nutritional and chemopreventive anti-cancer agents specifically increase the
expression of p27Kip1 protein without directly affecting the expression of any
other cell cycle regulatory proteins. On the other hand, pro-cancer agents
(like glucose, insulin and other growth factors frequently seen in obesity
and/or diabetes) specifically decrease the expression of p27Kip1 protein
without directly affecting the expression of any other cell cycle regulatory
proteins. Unlike expression of any other cell cycle regulatory proteins, expression
of p27Kip1 protein is very unusual. The mRNA of p27Kip1 has a very long and
unusual 5’-untranslated region (from -575 to -1 in human). It appears that the
5’-untranslated region of p27Kip1 mRNA forms two alternative secondary structures. One increases the expression of p27Kip1 protein when anti-cancer agents
are added and another decrease the expression of p27K1p1 when pro-cancer agents
are added. For this short concept proposal, Dr. Albert Einstein’s “visualized
thought experiments (German: Gedanken experiment)” were used as a fundamental
tool for understanding how either anti- or pro-cancer agents bring the primary
structure of the 5’-untranslated region of p27Kip1 mRNA into two alternative
secondary structures, thereby either increasing or decreasing, respectively, the
translation initiation of p27Kip1 protein.