Study reveals how fusion protein triggers cancer

Study reveals how fusion protein triggers cancer


(gentle piano music) – The key finding of our study is the identification of a new mechanism, by which a type of cancer called
B-cell lymphoma can happen. We have been stundying a
specific type of lymphoma called MALT lymphoma. And in the sub-set of MALT lymphomas, the cancer cells actually possess a, what’s called a fusion protein. This fusion protein is abnormal and it consists of one part of one protein fused to another part, and
the two parts of the API2 and the MALT1. And when these two parts are fused, they actually take on a
new and dangerous activity. What happens is, the API2
part of the fusion attracts an enzyme called NIK. And when NIK is attracted to the fusion, the MALT1 part of the fusion
then cuts NIK into two pieces. You might think that
cutting NIK into two pieces destroys NIK, but instead,
cutting NIK into two pieces actually makes NIK super powerful. What happens is when NIK is actually cut by this fusion protein, the
cutting removes what we call a regulatory portion, and when the regulatory
portion of NIK is removed, then it’s activity is
let loose in the cell and it acts somewhat like a renegade, and when you have excessive
unchecked NIK in a cell, that actually promotes the growth and the proliferation of the cell. – So NIK is a, what’s known as a Kinase. It’s a type of enzyme that’s capable of altering the function and
properties of other proteins in the cell, and they can have a number of different consequences. One of the consequences for certain Kinases in
particular NIK is the ability to affect whether a cell lives or dies, whether it multiplies,
whether it survives and grows. And one of the reasons
that this is especially exciting to us is that
two activities here, the ability of NIK as an enzyme to act as a Kinase within a cell and the ability of the
API2-MALT1 fusion protein to cleave NIK into two pieces, are both activities that are considered by the pharmaceutical
industry as drug-able. That is, those are two types of activities that historically the
pharmaceutical industry has been successful in developing drugs to block those types of activities. So, we think that we now have two sites to go after in terms of developing pharmaceuticals to combat MALT lymphoma. We’re very optimistic
that eventually we could, in the pharmaceutical
industry, could work to develop drugs that could target those activities. We’re not there yet, but we
have something to go after.