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A Potentially Dangerous Molecule On The Loose

 
  September, 3 2008 7:21
your information resource in human molecular genetics
 
     

Ubiquitin is a small protein that is used to tag other proteins inside the cell - among other things, to earmark it for localization to a particular cellular compartment. A paper in Nature reveals how losing this tag can cause a protein called PTEN to break loose from the cell nucleus and stop it carrying out its normal function of nipping potential cancers in the bud.

Pier Paolo Pandolfi and colleagues show that an enzyme agent known as HAUSP is responsible for removing PTEN's ubiquitin tag - if for any reason HAUSP becomes overactive, this deubiquitinylation will drive PTEN out of the cell nucleus and cause its important tumour-suppressing ability to be lost. Under these circumstances, human prostate cancer, for example, rapidly takes off.

The team found that another molecule in the nucleus, PML, normally keeps PTEN in place by curtailing HAUSP?s overactivity. PML is therefore also a tumour suppressor, and can give rise to an acute form of leukaemia if it mutates into a form with disrupted activity.

Dissecting this network and discovering how it can go wrong in aggressive cancers raises the possibility of designing drugs to prevent the rogue relocation of PTEN and keep a humdrum housekeeping process from going haywire.

CONTACT

Pier Paolo Pandolfi (Beth Israel Deaconess Medical Center, Boston, MA, USA)
E-mail: ppandolf@bidmc.harvard.edu

Abstract available online.

(C) Nature press release.


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