# Role of MYC Acetylation in Cancer

> **NIH NIH R03** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2020 · $70,248

## Abstract

Overexpression of the MYC protein is oncogenic and commonly observed in cancer, and
its inhibition induces regression of tumors in animal models. Hence, MYC is considered
a promising target for cancer treatment. Besides overexpression, MYC can be
deregulated by additional mechanisms, including aberrant upstream signaling pathways
and posttranslational modifications (PTMs), such as phosphorylation, ubiquitination,
sumoylation and acetylation that may affect the turnover and activity of the MYC protein.
In particular, the functions of MYC acetylation in normal and cancer cells have remained
elusive and the current information is scarce and often controversial. We propose that
the limited progress and apparent discrepancies are due, in part, to (i) the fact that
different histone acetyltransferases (HATs) and deacetylases (HDACs) dynamically
remodel the acetyl marks on distinct lysine (K) residues of MYC in different contexts and
with different outcomes, (ii) the use of pan-acetyl-lysine antibodies that do not distinguish
MYC acetylation at different K residues, and (iii) the study of a limited number of in vitro
cell systems/conditions that often involve artificial overexpression of HATs and may not
model the signaling mechanisms leading to MYC acetylation endogenously in normal
cellular contexts or in tumor cells. Hence, the relevance of MYC acetylation to normal
cell biology and/or cancer development has remained largely unknown. Our laboratory
has identified distinct K residues of MYC that are acetylated by different HATs and are
important for specific MYC functions in selective gene regulation and transformation of
rodent fibroblasts. We hypothesize that MYC acetylation is under tight regulatory control
in normal cells but is deregulated in tumor-derived cancer cells and influences the
oncogenic/transformation activity of MYC in human cells. To test this, Aim1 will
determine whether MYC acetylation is deregulated in cancer cells by analyzing a panel
of normal and cancer cell lines with acetyl-lysine site-specific antibodies and will identify
specific histone deacetylase pathways that may influence site-specific MYC acetylation.
Aim 2 will investigate the function of specific acetyl-lysine residues in MYC-dependent
transformation of human cells and in the maintenance of the transformed phenotype of
tumor-derived cancer cells. This project may uncover for the first time a deregulated
acetylation of MYC at specific residues in cancer cells and establish the role of these
acetylated residues in MYC-dependent transformation of human cells.

## Key facts

- **NIH application ID:** 10020361
- **Project number:** 5R03CA230843-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** ERNEST MARTINEZ
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $70,248
- **Award type:** 5
- **Project period:** 2019-09-18 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10020361

## Citation

> US National Institutes of Health, RePORTER application 10020361, Role of MYC Acetylation in Cancer (5R03CA230843-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10020361. Licensed CC0.

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