One of the most important tumor
suppressors, p53, stops healthy cells from becoming cancerous. It has previously been described as the 'guardian of the genome' and voted
'Molecule of the Year' in 1993, and is one of the most important
proteins regulating cell growth.
p53 is also a major focus for oncology research.
It is a protein that has the ability to interrupt the cell cycle and
block the division of diseased cells.
‘Tumor suppressor p53 accumulates in liver after food withdrawal. p53 in liver plays a crucial role in the body's metabolic adaptation to starvation.’
Researchers from CharitÚ - Universitńtsmedizin Berlin, the Medical
University of Graz and the German Institute of Human Nutrition in
Potsdam-Rehbruecke have found that p53 accumulates in liver after food withdrawal. They also show
that p53 in liver plays a crucial role in the body's metabolic
adaptation to starvation.
These findings may provide the foundation for
the development of new treatment options for patients with metabolic or
oncologic disorders. Results of this study have been published in The FASEB Journal
In order to better understand the physiological regulation of p53, the researchers around Prof. Dr. Michael
Schupp from CharitÚ's Institute of Pharmacology studied the regulation
and function of p53 in normal, healthy cells. After withholding food
from mice for several hours, the researchers were able to show that p53
protein accumulates in the liver.
In order to determine which type of
liver cells cause this accumulation, the researchers repeated the
experiment using cultured hepatocytes. They found that the
starvation-induced accumulation of p53 was indeed detectable in
hepatocytes, irrespective of whether these cells were of mouse or human
"Our data also suggest that the accumulation of p53 is mediated by a
cellular energy sensor, and that it is crucial for the metabolic
changes associated with starvation," explains Prof. Michael Schupp. The
researchers were able to show that mice with an acute inactivation of
the p53 gene in liver had difficulties in adapting their metabolisms to
"Food intake seems crucial in determining the protein levels
of p53 in liver, and p53 also plays an important role in normal liver
metabolism," says Prof. Schupp. The researchers are planning to study
whether their observations are limited to liver cells, or whether this
p53 accumulation also occurs in other tissues and organs.
concludes, "It would be interesting to conduct further experiments to
test whether the starvation-induced accumulation of p53 has an effect on
the development of specific forms of cancer, or whether certain ways of
timing meals might affect p53 protein levels in such a way as to
promote cancer development."