# Regulation and Function of SUMO Protein Modification -Equipment Supplement

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $229,690

## Abstract

PROJECT SUMMARY
Small ubiquitin related modifiers (SUMOs) function as posttranslational protein modifications and thereby
regulate nearly all essential cell functions. As such, sumoylation is linked to a variety of human diseases,
including cancer and neurodegenerative disorders, and there is great interest in targeting the SUMO pathway
for therapeutic purposes. Notably, the first phase I clinical trial of a SUMO inhibitor was recently approved for
cancer therapy. A more detailed understanding of basic molecular mechanisms regulating sumoylation and its
consequences on cell function, however, is needed to achieve the full potential of these efforts. In particular, an
ability to target specific branches of the SUMO pathway could allow for more precise therapies. Vertebrates
express multiple SUMO paralogs which could allow for such precision targeting. However, the unique
properties and functions of SUMO paralogs remain poorly understood. To address this gap in knowledge, we
are taking advantage of recently developed SUMO1 and SUMO2 knockout cell lines to define and characterize
the specific functions and molecular mechanisms of action of these two paralogs. Aims of our proposal include:
(1) We will obtain support for the hypothesis that SUMO1 and SUMO2 function as unique signals with non-
redundant roles in regulating distinct cellular processes. This will be achieved through characterization of
paralog-specific phenotypes we have identified in SUMO1 and SUMO2 knockout cell lines, including changes
in gene expression, cell morphology, defects in proteostasis and hypersensitivities to cell stress. (2) We will
test multiple hypotheses to reveal the molecular basis for non-redundant functions of SUMO1 and SUMO2.
Hypotheses concerning the function of chain formation and selective non-covalent interactions with effector
proteins will be explored through rescue of knockout cell phenotypes using a panel of SUMO1 and SUMO2
mutant proteins. (3) We will test the hypothesis that phenotypic changes observed in SUMO1 and SUMO2
knockout cell lines are due in part to paralog-specific effects on gene expression. Results from our studies will
provide a comprehensive understanding of the unique, paralog-specific functions of SUMO1 and SUMO2 and
vital insights required to target specific branches of the SUMO pathway for therapeutic purposes.

## Key facts

- **NIH application ID:** 10581055
- **Project number:** 3R01GM060980-19S2
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** MICHAEL J. MATUNIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $229,690
- **Award type:** 3
- **Project period:** 2020-03-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10581055

## Citation

> US National Institutes of Health, RePORTER application 10581055, Regulation and Function of SUMO Protein Modification -Equipment Supplement (3R01GM060980-19S2). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10581055. Licensed CC0.

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