Researchers at Texas A&M University have identified key components of a cellular pathway that helps certain cancer cells survive treatment, potentially offering a new target for more effective therapies. The findings were published in Nature Communications.
The study focuses on a protein called URM1, which has been conserved across evolution from yeast to humans. While scientists previously knew URM1 played a role in stress response, the specific molecular machinery controlling this pathway in human cells was not fully understood.
Led by Dr. Wenshe Liu, Regents Professor and Harry E. Bovay, Jr. Chair in chemistry in the College of Arts and Sciences, the team developed a specialized molecular probe to capture proteins involved in URM1 activity.
Using this tool, researchers identified two enzymes, NAE1/UBA3 and UBE2M, that drive the URM1 modification process. The study demonstrated that disrupting either enzyme sharply reduced URM1 activity. This effect was also observed when cells were treated with compounds that inhibit these enzymes, confirming their role as central regulators of the pathway.
The research showed that oxidative stress strongly activates URM1. Oxidative stress is a form of molecular damage triggered by normal metabolism and many cancer treatments. Many anticancer drugs work by overwhelming tumor cells with such damage to prevent them from surviving or growing. Understanding how cells adapt to these conditions may reveal ways to enhance treatment efficacy.
