# SCF Ubiquitin Ligases in Cell Cycle Control and Chromosome Stability

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $301,840

## Abstract

PROJECT SUMMARY ABSTRACT
Targeted protein degradation controlled by the ubiquitin proteasome system is involved in virtually all aspects
of cellular physiology, including development, signal transduction and aging. In addition, dysfunction in
ubiquitin mediated protein degradation is causative in diseases ranging from cancer to neurodegenerative
disorders. E3 ligases impart selectivity on the ubiquitin system by specifying target proteins for ubiquitylation
and degradation. The Cullin RING E3 ligases (CRLs) represent the largest E3 family in humans. CRLs rely on
large families of substrate receptors to specify which substrates become ubiquitylated. Connecting E3 ligases
with their cognate substrates, akin to mapping kinase and transcription factor targets, represents the key
challenge to defining the function of specific enzymes, and provides mechanistic insight into the role of
individual enzymes in cellular homeostasis and disease. The Cullin ligase SCF/CRL1 utilizes a family of 69
substrate receptors termed F-box proteins. The SCF is essential for cell cycle progression, checkpoint function
and genome stability. This proposal is focused on Cyclin F, a cell cycle regulated substrate receptor, F-box
protein for the SCF. Using Cyclin F as a paradigm, we will interrogate the broader role of CRLs in cell cycle
control. By leveraging our expertise in biochemistry, cell and systems biology we will gain a deep
understanding of Cyclin F function, and by extension the CRLs, in cell proliferation and genome stability, and
its potential contribution to malignancies.

## Key facts

- **NIH application ID:** 9996715
- **Project number:** 5R01GM120309-05
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Michael James Emanuele
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $301,840
- **Award type:** 5
- **Project period:** 2016-09-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9996715

## Citation

> US National Institutes of Health, RePORTER application 9996715, SCF Ubiquitin Ligases in Cell Cycle Control and Chromosome Stability (5R01GM120309-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9996715. Licensed CC0.

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