Isoform alterations in the ubiquitination machinery impacting gastrointestinal malignancies.

Autor: Kasturirangan S; Departments of Radiation Oncology, University of Michigan, Ann Arbor, MI, 48109, USA., Nancarrow DJ; Surgery - Section of Thoracic Surgery, University of Michigan, Ann Arbor, MI, 48109, USA., Shah A; Departments of Radiation Oncology, University of Michigan, Ann Arbor, MI, 48109, USA.; Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA., Lagisetty KH; Surgery - Section of Thoracic Surgery, University of Michigan, Ann Arbor, MI, 48109, USA., Lawrence TS; Departments of Radiation Oncology, University of Michigan, Ann Arbor, MI, 48109, USA., Beer DG; Surgery - Section of Thoracic Surgery, University of Michigan, Ann Arbor, MI, 48109, USA., Ray D; Departments of Radiation Oncology, University of Michigan, Ann Arbor, MI, 48109, USA. dipray@umich.edu.
Jazyk: angličtina
Zdroj: Cell death & disease [Cell Death Dis] 2024 Mar 08; Vol. 15 (3), pp. 194. Date of Electronic Publication: 2024 Mar 08.
DOI: 10.1038/s41419-024-06575-z
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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