# Inositol hexakisphosphate regulation of N-terminal acetyltransfearases

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2020 · $392,500

## Abstract

Project Summary
The overarching goal of this competing renewal grant is the elucidation of signaling pathways and the
mechanisms by which cells elicit selective responses to changes in their environment. Intracellular signaling
pathways, such as inositol phosphate (IP) messengers, are key regulators of biology and inborn errors in IP
networks result in disease. Over eighty genes are dedicated to the synthesis and breakdown of IP
messengers. While much is know about IP metabolism, less information is available as to how the ensemble
of dozens of IP molecules are decoded: that is, what are the receptors and how does IP binding alter their
function? Our laboratory has developed a new method for identifying decoders of IP signals and has made a
key discovery that inositol hexakisphosphate (IP6) is a structurally bound component and regulator of several
members of the ancient family of N-terminal acetyltransferases, known as NATs. The focus of this proposal is
to rigorously define the mechanisms by which IP6 and other metabolites influence NAT structure and function,
and ultimately alter protein N-terminal acetylation in normal and disease cellular states. The work outlined in
this proposal will contribute fundamental insights into how cells use lipid-derived inositol messengers to
enhance regulation, specificity and complexity of signaling biology.

## Key facts

- **NIH application ID:** 9927656
- **Project number:** 5R01GM124404-04
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** John D. York
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $392,500
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9927656

## Citation

> US National Institutes of Health, RePORTER application 9927656, Inositol hexakisphosphate regulation of N-terminal acetyltransfearases (5R01GM124404-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9927656. Licensed CC0.

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