Elucidating the Role of C16orf72 in the Cellular Stress Response Network

Summary

This project aims to elucidate the role of the C16orf72 protein in the cellular stress response network, specifically its interaction with HUWE1, to understand its molecular mechanism and investigate its therapeutic potential in cancer.

What they want

The project will investigate how malignant cells maintain viability under various stressors by focusing on C16orf72, a previously uncharacterized protein, and its physical interaction with HUWE1, an E3 ligase. The overarching hypothesis is that C16orf72 mediates stress resilience by promoting HUWE1-mediated ubiquitination of critical proteins in stress response pathways. The long-term goals are to determine the molecular mechanism by which C16orf72 promotes cellular stress resilience and to investigate the therapeutic potential of blocking the C16orf72/HUWE1 axis in cancer cells.

Deliverables

Define the binding interface of C16orf72 and HUWE1 and test models of C16orf72 regulation of HUWE1 enzymatic activity (Aim 1)
Determine the substrates and specific modifications underlying the role of C16orf72 and HUWE1 in cellular stress resilience and canonical stress response signaling (Aim 2)
Determine the extent to which C16orf72 is required for in vivo tumorigenesis and the development of therapy resistance in breast cancer (Aim 3)

Technical requirements

Genome-scale fitness screening data analysis
Transcriptomic analysis
Ubiquitination phenotyping
In vivo tumorigenesis studies