# Temporal-spatial control of mitotic regulators by polySUMOylation

> **NIH NIH R01** · FLORIDA STATE UNIVERSITY · 2023 · $330,839

## Abstract

Abstract
SUMOylation is an essential post-translational modification that adds small ubiquitin-like modifiers (SUMO) to
protein lysine residues. SUMOylation regulates many cellular functions, including cell proliferation, DNA repair,
and stress response. Deregulation of SUMOylation contributes to genome instability and cancer development.
Attachment of single SUMO to proteins often creates scaffolds to nucleate macromolecular interactions. On the
other hand, attachment of chains of SUMO (polySUMOylation) often triggers protein ubiquitination and extraction
from a macromolecular complex. Recent works demonstrate polySUMO-dependent relocation of damaged DNA,
which facilitates damage repair. However, the function of protein polySUMOylation and its regulation during cell
cycle remain poorly defined. Our long-term goal is to uncover the molecular mechanisms that control genome
stability to provide fundamental knowledge that will help develop treatment strategies for diseases resulting from
genome instability, such as cancer. The objective of this project is to investigate how polySUMOylation controls
the relocation of two key mitotic regulators during the cell cycle: the RENT (regulator of nucleolar silencing and
telophase) critical for mitotic exit, and the CPC (chromosomal passenger complex), essential for chromosome
bipolar attachment. We recently found that polySUMOylation induction in yeast cells triggers relocation of these
two critical mitotic regulators. Our preliminary data support the central hypothesis that polySUMOylation
promotes relocation of some key mitotic regulators for successful anaphase initiation, and activation of polo-like
kinase triggers polySUMOylation by phosphorylating a deSUMOylase. Our objective will be attained via the
following specific aims: 1) Elucidate the mechanism of polySUMOylation-triggered nucleolar protein
delocalization that promotes mitotic exit. 2) Determine how polySUMOylation of CPC subunits promotes CPC
translocation. 3) Investigate the temporal control mechanism for polySUMOylation during the cell cycle. To test
our hypothesis and achieve our aims, we will combine budding yeast genetics, cell biology, and biochemistry.
Successful completion of this research will provide a comprehensive understanding of how polySUMOylation
controls subcellular localization of protein complexes in the context of cell cycle. Given the exceptional
conservation of both the SUMO system and the cell cycle machinery, principles proved in budding yeast are
highly likely to translate to human and other eukaryotes. The results will have an important positive impact on
the cell biology field because they will uncover new mechanisms critical for genome stability and unveil new
targets for cancer diagnosis and therapy.

## Key facts

- **NIH application ID:** 10718546
- **Project number:** 1R01GM151447-01
- **Recipient organization:** FLORIDA STATE UNIVERSITY
- **Principal Investigator:** Yanchang Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $330,839
- **Award type:** 1
- **Project period:** 2023-09-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10718546

## Citation

> US National Institutes of Health, RePORTER application 10718546, Temporal-spatial control of mitotic regulators by polySUMOylation (1R01GM151447-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10718546. Licensed CC0.

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