E3 Ubiquitin Ligases as Molecular Machines and Platforms for Drug Development

Ioris, Rafael Maciel; Ferris, Katherine; D’Angiolella, Vincenzo

doi:10.1002/9783527836208.ch3

Cited by 1 publication

(1 citation statement)

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“…Ubiquitin-mediated protein degradation plays a critical role in regulating many diverse cellular processes and participates in both physiological and pathological processes of breast cancer. This regulatory system uses a series of enzymes to transfer ubiquitin molecules to their substrates to target them for destruction through proteasome machinery 14 – 16 . Combining inhibitors that target the 26S proteasome with other drugs has demonstrated promising therapeutic effects in the clinical management of breast cancer with novel prognostic biomarkers associated with the UPS 11 , 12 .…”

Section: Introductionmentioning

confidence: 99%

Prognostic potential of CUL3 ligase with differential roles in luminal A and basal type breast cancer tumors

Pantazi,

Miklós,

Smith

et al. 2024

Sci Rep

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Breast cancer is a prevalent and significant cause of mortality in women, and manifests as six molecular subtypes. Its further histologic classification into non-invasive ductal or lobular carcinoma (DCIS) and invasive carcinoma (ILC or IDC) underscores its heterogeneity. The ubiquitin–proteasome system plays a crucial role in breast cancer, with inhibitors targeting the 26S proteasome showing promise in clinical treatment. The Cullin-RING ubiquitin ligases, including CUL3, have direct links to breast cancer. This study focuses on CUL3 as a potential biomarker, leveraging high-throughput sequencing, gene expression profiling, experimental and data analysis tools. Through comprehensive analysis using databases like GEPIA2 and UALCAN, as well as TCGA datasets, CUL3's expression and its association with prognostic values were assessed. Additionally, the impact of CUL3 overexpression was explored in MCF-7 and MDA-MB-231 breast cancer cell lines, revealing distinct differences in molecular and phenotypic characteristics. We further profiled its expression and localization in breast cancer tissues identifying prominent differences between luminal A and TNBC tumors. Conclusively, CUL3 was found to be associated with cell cycle progression, and DNA damage response, exhibiting diverse roles depending on the tumor's molecular type. It exhibits a tendency to act as an oncogene in triple-negative tumors and as a tumor suppressor in luminal A types, suggesting a potential significance in breast cancer progression and therapeutic directions.

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