Study finds a new potential therapeutic target for cancer

New Delhi . (India Science Wire): The transfer of genetic information in the intact
form to the progeny is the cornerstone of the perpetuation of life on earth. However, the DNA
molecules that store this genetic information are susceptible to damage caused by many
internal and external factors that cells are frequently exposed to. Such genotoxic stress
experienced by the cell is one of the main factors contributing to the development of cancer.
Organisms have evolved cellular mechanisms that trigger a DNA damage response and repair
system, which helps prevent cancer development under normal circumstances. But if there
are defects in this, they can lead to cancer. The various components of the system have,
therefore, been the objects of research aimed at understanding the biology of cancer and
identifying therapeutic targets.
One such molecule of interest is a protein called “β-TrCP”, which controls many cellular
processes including DNA damage response. In humans, there are two forms of this protein, β-
TrCP1 and β-TrCP2, whose deregulation has been associated with many diseases, including
cancer.
Studies have shown that while β-TrCP1 can act as a tumor suppressor molecule, β-TrCP2 has
the potential to act as an oncogene. Tumor suppressors protect the genome from damage-
causing factors, whereas oncogenes counter this tumor suppressor function and allow
genetically abnormal (cancer) cells to grow. This raises questions as to whether β-TrCP1 and
β-TrCP2 molecules interact with each other, and if so, how do they do it.
A new study by a team of scientists at the National Centre for Cell Science (DBT-NCCS) in
Pune, an autonomous institute of the Department of Biotechnology (DBT), the Government
of India led by Dr. Manas Kumar Santra has gained some insights into this.
It has shown for the first time that β-TrCP1 and β-TrCP2 communicate with each other and
show cross-regulation during DNA damage response. They have established that when the
cell experiences genotoxic stress, β-TrCP1 tries to inactivate the function of β-TrCP2 so as to
activate p53, another important tumour-suppressor protein considered as a “guardian of the
genome”, thus protecting the cell from DNA damage and cancer development.
Their study has thus revealed that the β-TrCP1may be explored as a therapeutic agent to fight
cancer. The study team has published a report on its findings in the journal, Journal of
Biological Chemistry (JBC).

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