# Targeting RNF114 for Cancer Therapy and Targeted Protein Degradation

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $28,075

## Abstract

Natural products have been a prolific source of therapeutics for combatting cancers, including the widely-used
breast cancer drug taxol produced by the bark of the Pacific yew that acts through targeting tubulin to impair
breast cancer pathogenicity. While there are countless natural products derived from plants, microbes, and
other living organisms that have been shown to exert anti-cancer activity, the mechanism of action of most of
these natural products remain poorly understood. One such natural product is nimbolide, a triterpenoid
obtained from Azadirachta indica or neem, that has been shown by many groups to exert anti-cancer activity
against multiple different types of cancers, including breast cancers, hepatocellular carcinomas, colon cancers,
and renal cell carcinomas. While this natural product possesses compelling anti-cancer properties, the direct
targets remain poorly understood. I have used an innovative chemoproteomic platform termed activity-
based protein profiling (ABPP), which uses reactivity-based chemical probes to map reactive,
functional, and druggable hotspots in complex proteomes, to map the proteome-wide ligandable
hotspots targeted by the anti-cancer natural product nimbolide in breast cancer cells. My preliminary
data using ABPP indicate that nimbolide selectively targets C8 on the E3 ubiquitin ligase RNF114 in 231MFP
triple-negative breast cancer (TNBC) cells, leading to impaired ubiquitination of the tumor suppressor p21
through an impairment in the ability of RNF114 to recognize its protein substrates. This in-turn leads to an
elevation in p21 levels, leading to impaired breast cancer cell pathogenicity. In this proposal, I will use
innovative chemical biology approaches to determine the anti-cancer mechanisms of nimbolide and
characterize RNF114 as a target for cancer therapy and for targeted protein degradation applications.

## Key facts

- **NIH application ID:** 9889798
- **Project number:** 5F31CA239327-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Jessica Nichole Spradlin
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $28,075
- **Award type:** 5
- **Project period:** 2019-03-01 → 2020-09-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9889798

## Citation

> US National Institutes of Health, RePORTER application 9889798, Targeting RNF114 for Cancer Therapy and Targeted Protein Degradation (5F31CA239327-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9889798. Licensed CC0.

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