# Protein Acylation and Methylation Mechanisms_Administrative Supplement

> **NIH NIH R37** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $178,465

## Abstract

Project Summary
This proposal GM62437 combines the use of chemical approaches, enzymologic
analysis, and cellular studies to enhance our understanding of enzymes regulating
protein acylation and methylation. It is now well-accepted that post-translational
modifications (PTMs) involving lysine acetylation/acylation and reversible
methylation on histones and other proteins are central to epigenetics. Such
epigenetic modifying enzymes are viewed as attractive drug targets for cancer and
other diseases. Although there has been increasing efforts to understand the
mechanisms and functions of these PTMs and the enzymes that catalyze them, there
are major gaps in our understanding in these areas. Filling these gaps has the
potential to provide a clearer understanding of basic biomedical processes and has
the opportunity to enhance the development of novel therapeutic approaches and
disease diagnostic strategies. There are three Specific Aims in the current proposal:
1) Determine the roles of p300/CBP acetyltransferase activity in cellular pathways.
We will develop and employ new chemical tools that target the p300/CBP HAT
domain and bromodomain and examine these effects of these on cell growth,
protein acetylation, signaling, and gene expression. 2) Elucidate the mechanisms of
the LSD1 and HDAC1 activities in the CoREST complex and develop inhibitors of
these activities in the CoREST complex. We will employ a purified CoREST complex
and semiynethtic nucleosomes in biochemical and structural studies and design
small molecule LSD1 and dual action LSD1/HDAC1 inhibitors for cellular studies. 3)
Devise methods for the synthesis of acyl-Lys mimics and incorporate these into
proteins for enhancing our understanding of acyl-Lys as PTMs. We will use a Cys
modification stratgey to introduce hydrazino-Lys acylation mimics into proteins and
study their biochemical properties. We believe that this research effort has the
potential to greatly expand our knowledge of protein post-translational
modification mechanisms and functions and identify new therapeutic opportunities
for treating metabolic and neoplastic diseases.

## Key facts

- **NIH application ID:** 10135582
- **Project number:** 3R37GM062437-21S1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** PHILIP A COLE
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $178,465
- **Award type:** 3
- **Project period:** 2001-02-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135582

## Citation

> US National Institutes of Health, RePORTER application 10135582, Protein Acylation and Methylation Mechanisms_Administrative Supplement (3R37GM062437-21S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10135582. Licensed CC0.

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