# Mechanism of p53-dependent Tumor Suppression

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $433,586

## Abstract

Project Summary/Abstract
p53 tumor suppressor is frequently mutated in cancer, and mutant p53 is an oncogene. Upon exposure
to a stress signal, such as DNA damage, p53 transcription factor is activated and then induces an array of
pro-survival and pro-death genes. Among these is Rbm38, a RNA-binding protein. Interestingly, we
showed that Rbm38 represses p53 mRNA translation by preventing eIF4E from binding to p53 m7G cap.
Thus, p53 and Rbm38 constitutes a feedback loop. To determine the significance of the p53-Rbm38
loop, we showed that:(1) phosphorylation of serine-195 and substitution of S195 with aspartic acid
(S195D) prevent Rbm38 from interacting with eIF4E, which converts Rbm38 from a repressor to an
activator of p53 translation; (2) an 8-aa peptide derived from Rbm38 (Pep8: YPYAAS195PA) and a 23-
aa peptide derived from eIF4E (Pep23: aa 195-217) are able to disrupt the Rbm38-eIF4E complex to
increase p53 expression. These observations prompt us to hypothesize that the Rbm38-eIF4E pathway,
which is regulated by S195 phosphorylation and mutations in Rbm38, plays a critical role in p53-
mediated tumor suppression. To test this, we will determine: (1) how p53-dependent tumor suppression
is regulated by the Rbm38-eIF4E pathway; (2) whether the Rbm38-eIF4E pathway can be targeted to
kill tumor cells carrying wild-type p53.

## Key facts

- **NIH application ID:** 10817124
- **Project number:** 5R01CA250338-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Xinbin Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $433,586
- **Award type:** 5
- **Project period:** 2020-03-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10817124

## Citation

> US National Institutes of Health, RePORTER application 10817124, Mechanism of p53-dependent Tumor Suppression (5R01CA250338-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10817124. Licensed CC0.

---

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