New Delhi, September 24 : In a new developmentin the
area of cancer research, scientists at Delhi-based National Institute of
Immunology (NII) have found a way to stop the degradation of a protein called
p53 that prevents cancer cells from proliferating and forming tumours in the
p53 is one of
the most well studied proteins in cancer biology. Like all
proteins, its levels and activity are tightly controlled andthey go through
cycles of birth-existence-death: the protein is synthesised, it does its
function and then it is degraded. When
required, the protein is re-synthesised and the cycle keeps repeating.
Scientists across the world have been trying to find
out how the level of p53 is regulated and what arethe mechanisms underlying its
degradation. The team of scientists at NII havenow have shown that a protein called
FBW7 is responsible for degradingp53.Itdegrades not only the wild type p53 but
also mutant p53version, whichis involved in tumour promotion. As a validation
of their finding, researchers haveshown that the half-life of p53 is increased
andits function as tumorsuppressor got enhanced in cancer cells that lacked
The team has also worked out the mechanistic details
of how FBW7a recognizes p53 and degrades it.Further, they have showed that the
degradation happens as a result of damage to DNA induced by radiation and chemotherapy.
Interestingly, FBW7 expression itself is dependent on p53 and it gets induced
when cancer cells are exposed to DNA-damaging events. This indicates the
presence of auto-regulatory loop in cells which tightly regulates the amount of
p53 required to be present in the cells at any particular time.
“The results from our research provide
novel ways of improving tumor regression by improving the function of p53 by
stabilizing its levels. This could be achieved by using a mutant of p53, which
will not be degraded by FBW7α and may accentuate the therapeutic potential. Future
work is needed to build on this startegy to find clinical application,”
leader of the research team, while speaking to India
The study results have been published in the
Journal of Biological Chemistry. The team included VivekTripathi, Ekjot Kaur, SuhasSampatKharat,
Mansoor Hussain, ArunPrasathDamodaran and Swati Kulshrestha. The work was
supported the Department of Biotechnology, Council of Scientific and Industrial
Research, Science and Engineering Research Board and Department of Science and Technology.
(India Science Wire)
By Sunderarajan Padmanabhan
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