# Cytokinesis staging mechanisms

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $391,360

## Abstract

PROJECT SUMMARY
Eukaryotic
appropriately
commence
daughter
carcinogenesis
processes
cytokinesis
cell division requires dependency relationships in which late events start only after early ones are
 completed. During cytokinesis, for example, distinct large-scale morphological processes
in precise and consistent order to accomplish architectural reorganization that produces two
cells. Failure of mechanical division of cells can drastically affect genome stability, contributing to
and other important human maladies. mechanisms that coordinate cytokinetic
are incompletely understood, and a subject of intense research interest. Notably, machinery of
and regulators currently known to control it are highly conserved. Working in budding yeast, we
Regulatory
have discovered a system that blocks late events of cytokinesis when early ones are delayed or defective,
allowing time for corrective mechanisms to function. This “checkpoint” pathway, termed “Enforcement of
Cytokinesis Order” (ECO), works by stabilizing a multi-motif protein that blocks a cytokinesis-specific secretion
function of the Ndr/Lats protein kinase Cbk1, a key component of a highly conserved “Ndr-hippo” signaling
system.
Hippo signaling pathways are crucial regulators of morphogenesis, proliferation, and differentiation of
eukaryotic cells; Ndr/Lats kinases are their downstream-most signaling components. Our prior research
contributed crucial analysis for understanding of these systems. We were was among the first to describe
specific functions of a hippo signaling system in vivo, defined the distinctive Ndr kinase phosphorylation motif,
reported the first canonical substrate docking by an AGC-family protein kinase, and contributed the first and
only crystal structure of an Ndr/Lats kinase bound to a Mob co-activator.
This project seeks to determine how the checkpoint mechanism we discovered blocks secretion of late
cytokinesis proteins when early stages of the process are defective. It will include exploration of in vivo
docking interactions with cytokinesis regulators, assessment of secretion organization during cytokinesis, and
evaluation of the importance of Ndr-hippo regulation of key effector proteins of cytokinesis. We will also explore
the hypothesis that human Ndr-hippo pathways participate in control of late cytokinesis, using two different
approaches. In one, we will determine if human Ndr kinases engage in docking interactions with in vivo
phosphorylation targets, using a highly optimized phage display approach to identify possible peptide motifs
that interact with Ndr kinase – Mob co-activator complexes. We will use a new ligand footprinting method we
developed to map peptide motif associations. In another approach, we will determine if human Ndr-hippo
signaling functions in cytokinesis by constructing cell lines expressing only analog sensitive Ndr kinases. This
will allow rapid and reversible inhibition of these kinases in cells undergoing both normal and defective
cytokine...

## Key facts

- **NIH application ID:** 10163221
- **Project number:** 5R01GM137133-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** ERIC Lyle WEISS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $391,360
- **Award type:** 5
- **Project period:** 2020-05-12 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163221

## Citation

> US National Institutes of Health, RePORTER application 10163221, Cytokinesis staging mechanisms (5R01GM137133-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10163221. Licensed CC0.

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