# Role of E3 Ligase, UBR5, in Hematopoietic Differentiation and Lymphomagenesis

> **NIH NIH P20** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2021 · $333,538

## Abstract

Project Summary/Abstract: Role of E3 Ligase, UBR5, in Hematopoietic Differentiation and
Lymphomagenesis
Mantle cell lymphoma (MCL) is a rare and aggressive non-Hodgkin's lymphoma. Unfortunately, limited
therapies for MCL are currently available suggesting a need to further unravel molecular mechanisms
regulating transformation and progression of the disease. The majority of MCL patients have mutations leading
to overexpression of Cyclin D1 in the pre-B cell population, resulting in extensive proliferation and blocks in
differentiation originating in the mantle zone of the lymph node. Recently, next generation sequencing has
identified a number of novel mutations in MCL patients including the ubiquitin E3 ligase UBR5. E3 ubiquitin
ligases serve as the substrate recognizing component for protein degradation by the ubiquitin proteasome
system. Approximately 18% of MCL patients were found to have mutations within the HECT domain of UBR5,
which can accept and transfer ubiquitin molecules to the substrate. Interestingly, in hematopoietic lineages the
B-lymphoid populations including the pre-B cell compartment, highly express UBR5 compared to the myeloid
and T-lymphoid compartments. These findings suggest that understanding the role and interacting proteins of
UBR5 in hematopoiesis will provide insights to mantle cell lymphoma transformation, progression and possible
future therapeutics targets, in addition to basic understanding of hematopoietic cell specification.

## Key facts

- **NIH application ID:** 10117103
- **Project number:** 5P20GM121316-04
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Shannon Buckley
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $333,538
- **Award type:** 5
- **Project period:** 2018-03-16 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10117103

## Citation

> US National Institutes of Health, RePORTER application 10117103, Role of E3 Ligase, UBR5, in Hematopoietic Differentiation and Lymphomagenesis (5P20GM121316-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10117103. Licensed CC0.

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