# Oncogenic functions of mutant p53

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2024 · $314,415

## Abstract

Abstract
 The tumor suppressor gene, p53, has pleiotropic functions that quash tumor development.
One of its most important functions is to prevent the genome from sustaining DNA damage in
order to prevent the propagation of genetic lesions into daughter cells. Given the high degree of
genetic alterations in cancer, it is not surprising that p53 is frequently inactivated. The most
common form of genetic lesions in the p53 gene are point mutations in the DNA binding domain.
These missense mutations typically inactivate the p53’s tumor suppressor activity while
simultaneously generating an oncogenic protein. The presence of mutant p53 correlates with
increased chromosomal instability leading to loss of tumor suppressor genes and amplification of
oncogenes. It has become increasingly recognized that the cGAS/STING/TBK1/IRF3 innate
immune response signaling pathway plays a crucial role in detecting genetic alterations and
launching cell intrinsic and extrinsic responses to suppress aberrant cells that harbor genetic
defects. In this proposal, we that mutant p53 suppresses signaling through the cGAS/STING
pathway and thereby dictates how cells respond to its activation. We propose three aims to
determine the mechanism by which mutant p53 controls cGAS/STING signaling, and the cell
intrinsic and extrinsic consequences of modulation of this pathway. The completion of these
studies will help guide how to therapeutically approach cancers based on their p53 status.

## Key facts

- **NIH application ID:** 10791756
- **Project number:** 5R01CA166974-09
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Luis Alfonso Martinez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $314,415
- **Award type:** 5
- **Project period:** 2013-05-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10791756

## Citation

> US National Institutes of Health, RePORTER application 10791756, Oncogenic functions of mutant p53 (5R01CA166974-09). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10791756. Licensed CC0.

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