Researchers at The University of Texas M. D. Anderson Cancer Center have found that a tumour-suppressing protein, called KEAP1, destroys an important cancer-promoting enzyme.
KEAP1 snatches up the oncoprotein IKKß and tags it with molecules that condemn it to destruction, explained the researchers.
"KEAP1 is a recently discovered tumour suppressor, but how it works has not been known. IKKB is a known oncoprotein that promotes cancer in at least two different ways, but we did not know how it was regulated. We think we've answered both questions with this research," said senior author Dr. Mien-Chie Hung.
The researchers showed that KEAP1, short for the tongue-twisting Kelch-like ECH-associated protein 1, binds to IKKB and attaches molecules known as ubiquitins to the oncoprotein, which targets it for dissolution by the cell's proteasome complex.
They also showed that underexpression of KEAP1 is associated with poor survival among breast cancer patients, and that it's mutated and inactivated in some breast, liver, lung and colon tumours.
"KEAP1 underexpression or inactivation is involved in multiple cancers, so we are working now to identify its activation mechanism, which could lead to development of new anti-cancer drugs," said Hung.
He and his colleagues also want to know whether KEAP1 works on other known oncoproteins.
The study has been published in the journal Molecular Cell.