Francis Crick Institute scientists have discovered how two
molecules regulate autophagy - a recycling process used by cells to
maintain their health by removing harmful substances and to aid
survival under stresses including starvation.
The findings have possible implications for developing new
treatments for cancer.
Dr Sharon Tooze of the Crick (currently based at Lincoln's
Inn Fields) said: "In healthy cells autophagy is good for cells
and helps them perform their normal functions. However in cancer
cells, autophagy can be hijacked to allow cancer cells to survive
under adverse conditions. Understanding how autophagy can be
controlled will benefit human health by providing ways to control
autophagy in cancer cells, and hopefully kill cancer cells."
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WAC was discovered as a new molecule regulating autophagy that
binds to GM130, a molecule previously implicated in cancer. WAC
stops GM130 binding to a key autophagy molecule called GABARAP,
which allows GABARAP to move into the right place in the cell at
the right time for autophagy to occur.
The process involves controlling a collection of GABARAP
molecules at the centrosome - a structure near the centre of our
cells that is a 'master controller' of many important cellular
activities such as cell division and differentiation, and the
conversion of one cell type into another.
Dr Tooze said: "Abnormal centrosome structure and number has
been linked with cancer and other diseases.
"Our work provides a link between this essential autophagy
molecule, GABARAP, and the centrosome, and importantly implies that
the regulation of autophagy could be linked to the control of cell
division, growth and differentiation.
"The study's findings could provide a new avenue for therapies
affecting cell survival and tumour growth."
The paper, Activation of ULK Kinase and Autophagy by GABARAP Trafficking from
the Centrosome Is Regulated by WAC and GM130, is published inMolecular Cell.