# Effect of FABP5 oxidation on fatty acid binding and EGF signaling

> **NIH NIH F32** · BOSTON COLLEGE · 2020 · $23,839

## Abstract

Project Summary/Abstract
The epidermally-expressed fatty acid binding protein 5 (FABP5) is an intracellular fatty-acid transport protein
and a key component of lipid signaling pathways. FABP5 and the epidermal growth factor receptor (EGFR) are
both upregulated in a number of cancers including triple negative breast cancer and colorectal cancer.
Furthermore, knockdown of FABP5 results in decreased EGFR expression and EGF-induced metastatic
potential in triple negative breast cancer cells. In an unbiased proteomics screen for EGF-induced cysteine
oxidation, FABP5 cysteine 120 was identified as highly oxidized upon EGF treatment. The results of the screen
suggest that FABP5 C120 is reduced in the absence of EGF, but upon EGFR activation, when hydrogen
peroxide levels are known to increase within the cell, C120 becomes oxidized. Crystal structures of FABP5
have shown that C120 can form a disulfide bond with C127, proximal to the fatty acid binding pocket of FABP5.
The role of disulfide-bond formation on FABP5 function and EGF signaling has not been characterized
previously. Here we hypothesize that the EGF-induced formation of the C120-C127 disulfide bond is a
mechanism of redox-based EGF signal transduction. Furthermore, we propose that the reactive and redox-
active cysteine residues provide a handle for pharmacologically modulating the fatty-acid binding capacity of
FABP5 with covalent cysteine-reactive fragments. Therefore, we aim (1) to characterize the influence of
disulfide formation on FABP5 fatty acid binding; (2) to measure the impact of FABP5 disulfide formation on
EGF signal transduction and cellular cancer phenotypes; and (3) to explore the ligandability of C120/127 on
FABP5. In vitro fatty acid binding assays will be performed with oxidized WT FABP5, reduced WT FABP5, as
well as a C120S/C127S FABP5 mutant. Cell lines expressing WT FABP5 or the C120S/C127S mutant will be
generated and assayed for and EGF signaling and cancer phenotypes. Finally, a mass spectrometry-based
screen for covalent ligands of FABP5 C120/C127 will be performed in order to identify specific covalent
inhibitors of FABP5 fatty acid binding.

## Key facts

- **NIH application ID:** 9880287
- **Project number:** 5F32GM131615-02
- **Recipient organization:** BOSTON COLLEGE
- **Principal Investigator:** Jennifer C. Peeler
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $23,839
- **Award type:** 5
- **Project period:** 2019-03-01 → 2020-06-26

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9880287

## Citation

> US National Institutes of Health, RePORTER application 9880287, Effect of FABP5 oxidation on fatty acid binding and EGF signaling (5F32GM131615-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9880287. Licensed CC0.

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