# ELUCIDATING THE FUNCTION OF P53-MEDIATED IL17RB REPRESSION

> **NIH NIH R15** · ST. JOHN'S UNIVERSITY · 2024 · $492,000

## Abstract

ABSTRACT
In addition to its pivotal roles in regulating cell cycle arrest, apoptosis, DNA repair, and metabolism, the p53
tumor suppressor has been demonstrated to modulate innate immune and adaptive immune responses through
its crosstalk with key regulators of immune signaling pathways. The dysregulation of Interleukin 17 (IL17)
cytokine family and its receptors has been associated with many human diseases, notably inflammation and
cancer, crediting to their crucial roles in normal host immune responses. Particularly, Interleukin 17 Receptor B
(IL17RB) has been found to be overexpressed in various cancers through the activation of NFB, AKT, or ERK
signaling to promote tumorigenesis. Our preliminary results indicate that IL17RB is a p53 repression target and
repression of IL17RB sustains the p53 response. Additionally, activation of p53 by nutlin-3a or IL17RB depletion
decreases the expression of pro-inflammatory cytokine IL8 induced by lipopolysaccharide (LPS). The goal of
this application is to study the role of p53-mediated IL17RB repression in tumor suppression and inflammation
inhibition. We established systems of IL17RB repression, overexpression, and activation, that will enable
biochemical and cellular characterization as well as in-depth gene expression analyses to elucidate the
contribution of IL17RB repression to tumor suppressive and inflammation inhibitory function of p53. The
proposed work will not only allow us to gain a better understanding on how IL17RB links p53’s crosstalk with
other signaling pathways and how p53 attenuates oncogenic effects of chronic inflammation through repressing
IL17RB, but also provide a mechanistic basis for the development of novel anti-cancer strategies as well as
inflammation inhibitors. In addition, this project will enhance the research environment at St. John’s University
by providing undergraduate and graduate students with numerous opportunities to learn the fundamentals of
biomedical research.

## Key facts

- **NIH application ID:** 10796206
- **Project number:** 1R15CA287406-01
- **Recipient organization:** ST. JOHN'S UNIVERSITY
- **Principal Investigator:** Yan Zhu
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $492,000
- **Award type:** 1
- **Project period:** 2023-12-15 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10796206

## Citation

> US National Institutes of Health, RePORTER application 10796206, ELUCIDATING THE FUNCTION OF P53-MEDIATED IL17RB REPRESSION (1R15CA287406-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10796206. Licensed CC0.

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