Isoform Alterations in the Ubiquitination Machinery Impacting Gastrointestinal Malignancies

Authors

Srimathi Kasturirangan
Derek Nancarrow
Ayush Shah, Thomas Jefferson UniversityFollow
Kiran Lagisetty
Theodore Lawrence
David Beer
Dipankar Ray

Document Type

Article

Publication Date

3-8-2024

Comments

This article is the author's final published version in Cell Death and Disease, Volume 15, Issue 3, March 2024, Article number 194.

The published version is available at https://doi.org/10.1038/s41419-024-06575-z.

Copyright © The Author(s) 2024

Abstract

The advancement of RNAseq and isoform-specific expression platforms has led to the understanding that isoform changes can alter molecular signaling to promote tumorigenesis. An active area in cancer research is uncovering the roles of ubiquitination on spliceosome assembly contributing to transcript diversity and expression of alternative isoforms. However, the effects of isoform changes on functionality of ubiquitination machineries (E1, E2, E3, E4, and deubiquitinating (DUB) enzymes) influencing onco- and tumor suppressor protein stabilities is currently understudied. Characterizing these changes could be instrumental in improving cancer outcomes via the identification of novel biomarkers and targetable signaling pathways. In this review, we focus on highlighting reported examples of direct, protein-coded isoform variation of ubiquitination enzymes influencing cancer development and progression in gastrointestinal (GI) malignancies. We have used a semi-automated system for identifying relevant literature and applied established systems for isoform categorization and functional classification to help structure literature findings. The results are a comprehensive snapshot of known isoform changes that are significant to GI cancers, and a framework for readers to use to address isoform variation in their own research. One of the key findings is the potential influence that isoforms of the ubiquitination machinery have on oncoprotein stability.

Recommended Citation

Kasturirangan, Srimathi; Nancarrow, Derek; Shah, Ayush; Lagisetty, Kiran; Lawrence, Theodore; Beer, David; and Ray, Dipankar, "Isoform Alterations in the Ubiquitination Machinery Impacting Gastrointestinal Malignancies" (2024). Department of Medicine Faculty Papers. Paper 440.
https://jdc.jefferson.edu/medfp/440

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

38453895

Language

English