# Role of UBR7, a novel H2BK120 E3 ubiquitin ligase, in suppression of breast cancer

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $370,575

## Abstract

ABSTRACT
Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with no targeted treatment
available. Although we have made tremendous progress in regards to the genetic drivers of this disease, we
have limited understanding of the epigenomic alterations that drive specific molecular subtypes of breast
cancers. The epigenome consists of an array of chromatin modifications, which collectively form a dynamic
chromatin state that impinges upon gene expression networks critical for maintaining cellular identity.
Therefore, specific epigenomic alterations may act as drivers of different molecular phenotypes, however we
have limited understanding of how specific chromatin patterns may be associated with specific molecular
signatures such as basal-like breast cancer. Since epigenetic enzymes are targetable and epigenetic
processes are reversible in nature, they could prove to be excellent targets for novel therapeutic strategies
against specific molecular phenotypes. Our preliminary data suggests tumor suppressor activities for UBR7, a
novel histone modifier, in triple negative breast cancer. We show that UBR7 acts as a E3 ubiquitin ligase for
monoubiquitination of histone H2B at K120 residue and may transcriptionally regulate molecular signatures for
invasive breast cancers. These data provide rationale for in depth characterization of tumor-suppressor
function of UBR7 and identification of therapeutic vulnerabilities imparted by UBR7 loss. Our hypothesis is
that UBR7 is a potent tumor suppressor in triple negative breast and promotes invasive behavior in triple-
negative breast cancer partly by regulation of cadherin pathway. The objective of this proposal is to first
perform in depth characterization of UBR7 tumor-suppressor activity using mouse models, elucidation of
downstream cellular processes/pathways and identification of inhibitors/protein targets to inhibit in UBR7-low
triple-negative breast cancers. We aim to 1) characterize tumor-suppressor role of UBR7 and determine the
genetic context in which UBR7 loss promotes triple-negative breast cancers; 2) determine if UBR7 loss
promotes EMT and breast cancer metastasis by alteration of chromatin states and Cadherin genes; and 3)
determine genetic and pharmaceutical vulnerabilities of UBR7-deficient triple negative breast cancers. Overall,
our studies will provide significant advances in understanding role of epigenome in triple-negative breast
cancer tumor progression and define molecular mechanisms underlying contribution of new histone modifier to
cancer development.

## Key facts

- **NIH application ID:** 10124317
- **Project number:** 5R01CA226269-02
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Kunal Rai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $370,575
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10124317

## Citation

> US National Institutes of Health, RePORTER application 10124317, Role of UBR7, a novel H2BK120 E3 ubiquitin ligase, in suppression of breast cancer (5R01CA226269-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10124317. Licensed CC0.

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