# ESCRT and MIT Complexes in Cytokinesis

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $364,826

## Abstract

PROJECT SUMMARY/ABSTRACT
To divide, cells must faithfully partition their duplicated genomes (mitosis) and then separate (cytokinesis). The final
abscission step of cytokinesis is catalyzed by the ESCRT machinery, which severs the midbody to separate the nascent
daughter cells. This step is negatively regulated by the NoCut/abscission checkpoint in response to mitotic errors such as
intercellular DNA bridges or incomplete nuclear pore formation, providing cells with time to correct errors or mount
protective responses. NoCut failure therefore results in DNA damage and is linked to several types of cancer.
Within the midbody, ESCRT-III proteins form membrane-bound filaments that collaborate with VPS4 ATPases to constrict
and cut the membrane. These filaments also bind other MIT domain-containing cofactors that participate in NoCut and
abscission. We previously identified three classes of MIT enzymes with important cytokinetic functions: 1) ULK3 kinase,
which phosphorylates and inactivates ESCRT-III proteins, 2) VPS4s and related “meiotic clade” AAA ATPases, and 3) the
CAPN7 cysteine protease. We will now study how the latter two classes of MIT enzymes function during cytokinesis to
remodel ESCRT-III filaments (VPS4s), sever spindle microtubules (SPASTIN and KATANIN), or sustain NoCut signaling
and then promote abscission (CAPN7 and SPASTIN). We have also recently discovered a previously uncharacterized
cytoplasmic organelle, the Abscission Checkpoint Body (ACB), that contributes to NoCut abscission delay, apparently by
sequestering essential ESCRT abscission factors like ALIX away from the midbody. We will now elucidate how ACBs
form and help to regulate abscission timing. Our ultimate goal is to define how cells maintain NoCut signaling to prevent
premature abscission, and then sever the midbody to create separate daughter cells.

## Key facts

- **NIH application ID:** 10890831
- **Project number:** 5R01GM112080-10
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** CHRISTOPHER P. HILL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $364,826
- **Award type:** 5
- **Project period:** 2014-07-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10890831

## Citation

> US National Institutes of Health, RePORTER application 10890831, ESCRT and MIT Complexes in Cytokinesis (5R01GM112080-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10890831. Licensed CC0.

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