Nature Communication: Proteins that Make Difference between Cancerous and Healthy Cells Found

A recent study published in Nature Communication reveals how cancerous cells differ from healthy ones, which paves way for the development of novel strategies for the therapeutic intervention for difficult-to-treat cancers in the future.

 

An international research team discovered a “stop sign”- a mutated protein called PIP-stop, which is overused by tumor cells and can effectively prevent healthy cells from classifying in the way they are designed to.

 

“We have found that there are too many PIP-stops in breast cancer cell, leukemia, lymphoma, and neuroblastoma cells. This will disrupt protein function, and provide new ideas for the development of new drugs to inhibit the production of PIP-stop by targeting protein kinases,” said Michael Overduin, a cancer expert and biochemistry professor at the University of Alberta, who led the study.

 

The team called this protein PIP-stop because it can prevent proteins from interacting with lipid molecule PIP.

 

Mutation of the conserved PIP-stop residue Ser72 modulates membrane association

Fig1. Mutation of the conserved PIP-stop residue Ser72 modulates membrane association

 

Before this discovery, the researchers first solved the 3-dimensional structure of microtubule-connected protein SNX3, responsible for sorting, and SNX3 is crucial for the accurate localization of intracellular proteins.

 

By focusing on the SNX3 structure, the researchers discovered PIP-stop and studied how it inhibits protein function. PIP-stops are usually responsible for controlling how proteins bind to cell membranes.

 

There are too many PIP-stops in samples from cancer patients, which leads to the irregular growth of cancer cells. It has been found that a large number of proteins in a variety of cancer cells overuse similar PIP-stops, which can therefore also affect tumor growth.

 

“Our current goal is to design inhibitors that target over-activated kinases that create PIP-stop, and use this information to design drug molecules that inhibit tumor progression, especially those that currently lack effective therapies,” said Overduin.

 

 

Reference

Marc Lenoir et al, Phosphorylation of conserved phosphoinositide binding pocket regulates sorting nexin membrane targeting, Nature Communications (2018). DOI: 10.1038/s41467-018-03370-1