# Mechanism of P73-dependent Tumor Suppression

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $452,162

## Abstract

Project Summary/Abstract
p73, a member of the p53 family of tumor suppressors, is expressed from two promoters: the upstream
P1 promoter that produces TAp73 and the downstream P2 promoter that produces ΔNp73. Additionally,
p73 is expressed as six isoforms () through alternative splicing between exon 11-13. As a
transcription factor, we and others showed that TAp73 contains an activation domain similar to the first
activation domain (AD1) in p53. We also identified a unique activation domain in Np73. Thus,
TAp73 and Np73 are capable of inducing a distinct set of target genes. Consistent with its
transcriptional activity, mice deficient in TAp73 are prone to spontaneous tumors and accelerated aging
whereas mice deficient in Np73 are prone to neurological defects. However, compared to TA and N
isoforms, very little is known about p73 C-terminal isoforms and their activities in vivo. Now, by using
CRISPR-cas9 method to delete one or more exons in the p73 gene in cell lines and in mice, we are able
to systematically study the role of p73 C-terminal isoforms in vitro and in vivo. Our preliminary data
showed that various p73 C-terminal isoforms have distinct activities. Thus, we hypothesize that each
p73 C-terminal isoform has a unique function in tumor suppression and longevity. To test this, we will
determine: (1) C-terminal isoform-specific activities in cell growth and differentiation; (2) C-terminal
isoform-specific activities in tumor suppression and longevity; (3) C-terminal isoform-specific effects
on tumorigenesis in p53-deficient or mutant p53R270H knockin mice.

## Key facts

- **NIH application ID:** 10083713
- **Project number:** 5R01CA081237-22
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Xinbin Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $452,162
- **Award type:** 5
- **Project period:** 1999-05-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10083713

## Citation

> US National Institutes of Health, RePORTER application 10083713, Mechanism of P73-dependent Tumor Suppression (5R01CA081237-22). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10083713. Licensed CC0.

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