# The feedback loop between ferredoxin reductase and the p53 family in tumor suppression

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $410,152

## Abstract

Project Summary
The p53 family of tumor suppressors is consisted of p53, p63, and p73. The p53 family proteins
act as a tumor suppressor primarily through their transcriptional targets. We and others showed
that ferredoxin reductase (FDXR) is induced directly by p53, p63 and p73. Initial investigations
showed that ectopic expression of FDXR increases, whereas partial disruption of the FDXR gene
decreases, the sensitivity of tumor cells to DNA damage-induced apoptosis in a p53-dependent
manner. To investigate the biological function of FDXR, we carried out a pilot study by
generating FDXR-deficient cells and mouse models. We showed that FDXR deficiency
promotes iron regulatory protein 2 (IRP2) expression. We also showed that cells deficient in
FDXR exhibit iron overload in the mitochondria. Most interestingly, we showed that cells
deficient in FDXR are also deficient in p53 and p73 expression. In contrast, p63 expression is
increased in FDXR-deficient cells. Furthermore, FDXR+/- mice have a short lifespan along with
high incidence of spontaneous tumors. These observations prompt us to hypothesize that the
FDXR-p53 family pathway is necessary for tumor suppression. To test this, we will determine:
(1) how p53 is regulated by FDXR and the role of the FDXR-p53 loop in tumor suppression; (2)
how p63 is regulated by FDXR and the role of the FDXR-p63 loop in tumor suppression; (3)
how p73 is regulated by FDXR and the role of the FDXR-p73 loop in tumor suppression.

## Key facts

- **NIH application ID:** 9849761
- **Project number:** 5R01CA224433-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Xinbin Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $410,152
- **Award type:** 5
- **Project period:** 2018-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849761

## Citation

> US National Institutes of Health, RePORTER application 9849761, The feedback loop between ferredoxin reductase and the p53 family in tumor suppression (5R01CA224433-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9849761. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*