Abstract:
Introduction
It is well established now that (1) the risks of various types of cancer are significantly higher in obesity and/or type 2 diabetes. It is also well established now that (2} the risks of various types of cancer are significantly lower in caloric restriction.
The underlying molecular biological processes, however, appear to be very confusing. We now propose that the p27Kip1, a particular cell cycle repressor protein, appears to provide a consistent molecular biological mechanism of the risks of various of cancer in obesity, type 2 diabetes or caloric restriction.
Expression of p27Kip1 in Obesity, Type 2 Diabetes and Caloric Restriction
p27Kip1 is a cell cycle repressor protein expressed primarily in the late G1 phase of the cell cycle. Subsequent in vivo physiological studies and in vitro biochemical studies indicated that the expression of p27Kip1 is significantly decreased in obesity and/or type 2 diabetes. This suggested that the flood gate between G1 and S phase is open, the cell cycle goes faster, DNA replication increases in S phase and cell division increases in M phase.
In contrast to obesity and/or type 2 diabetes, expression of p27Kip1 is significantly increased in caloric restriction. This suggested that the flood gate between G1 and S phase is closed, the cell cycle goes slower, DNA replication decreases in S phase and cell division decreases in M phase. Please note that this types of change in the expression was never observed in any other cell cycle regulatory proteins.
Molecular Biological Mechanism of the Expression of p27Kip1 mRNA
Examinations of the primary RNA sequence of the p27Kip1 mRNA revealed the existence of a very unusual RNA sequence. This sequence spans from 5’-upstream negative position of 575 to negative position of 1. This sequence regulates the level of expression of p27Kip1 protein.
