# SUMO Modification and Cancer Therapy

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $486,964

## Abstract

Many enzymes catalyzing ubiquitin-like (Ubl) modifications have been identified as targets for
the therapeutic development of life-threatening human diseases that lack a cure. However, Ubl
modifications are poorly addressed by FDA approved drugs, highlighting the immense potential
to exploit this type of post-translational modification to address unmet medical needs.
Conjugation of Ubls to target proteins begins by activation of the C-terminus of a Ubl, a step
catalyzed by enzymes generally known as activating enzyme or E1. Several E1 enzymes,
including the SUMO-activating enzyme (SAE), have been validated as therapeutic targets by
animal models and by early phase clinical studies. Our recent discovery of a conserved
cryptic site on the SAE provides a paradigm-shifting allosteric approach to inhibit Ubl
activating enzymes. In the next funding period, we will further elucidate the mechanism of
the structure-activity relationship. Additionally, we will validate that the allosteric inhibition
approach we discovered reduces cancer drug resistance for targeting Ubl activating
enzymes. Furthermore, we will define the molecular mechanism of how SUMOylation
regulates type I IFN expression and validate that SAE inhibition is an effective approach to
induce anti-tumor immunity for immune cold colorectal cancers. The proposed studies build
on our scientific progress in the previous funding cycle and our more than 20-year
experience in studying SUMOylation. The proposed studies are expected to result in long-
lasting impacts that will spur innovation in targeting Ubl for therapeutic development and
result in new immune therapeutic strategies for immune cold tumors that do not respond to
current immune therapies and are high unmet needs, such as colorectal cancers.

## Key facts

- **NIH application ID:** 10833138
- **Project number:** 5R01CA265410-16
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Yuan Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $486,964
- **Award type:** 5
- **Project period:** 2021-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10833138

## Citation

> US National Institutes of Health, RePORTER application 10833138, SUMO Modification and Cancer Therapy (5R01CA265410-16). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10833138. Licensed CC0.

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