Many cellular processes rely on protein complexes assembled from multiple proteins, or subunits. This organization allows cells to respond rapidly to external signals by changing the composition of a complex to modulate its function for different needs. For instance, basal activity of a core catalytic enzyme may be modified based on the subunits present in the complex. RNA polymerase II, an enzyme that copies DNA into messenger RNA, is a complex made up of at least 10 different subunits that help regulate differential gene expression. One strategy by which cells regulate protein complex composition is through the eviction and destruction of individual subunits. Through a process called ubi...

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Many cellular processes rely on protein complexes assembled from multiple proteins, or subunits. This organization allows cells to respond rapidly to external signals by changing the composition of a complex to modulate its function for different needs. For instance, basal activity of a core catalytic enzyme may be modified based on the subunits present in the complex. RNA polymerase II, an enzyme that copies DNA into messenger RNA, is a complex made up of at least 10 different subunits that help regulate differential gene expression. One strategy by which cells regulate protein complex composition is through the eviction and destruction of individual subunits. Through a process called ubiquitylation, cells can target specific proteins for rapid elimination. As a result, cells can remove a complex's subunits for an expedited response to environmental stress or other stimuli. Errors in protein degradation can promote tumor development. For example, one of the most frequently mutated genes found in human cancers encodes a ubiquitylation enzyme that facilitates the destruction of protein complexes needed for cell growth and proliferation. As a new faculty member in the Department of Cell Biology at UT Southwestern Medical Center, Dr. Kevin Mark is interested in determining how ubiquitylation regulates the multisubunit protein complexes involved in gene expression and other critical cellular functions. With support from the CPRIT award, his research program seeks to understand: (1) how ubiquitylation remodels protein complexes to promote liver tumorigenesis, (2) how protein degradation regulates cellular stress response factors to alter liver tumor growth and (3) how small molecules can be used to harness the ubiquitylation system for targeted degradation of oncogenic proteins in cancer. Based on results from these studies, Dr. Mark aims to develop new therapeutic strategies to inhibit tumor growth in cancer patients.

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