# Mechanism of P73-dependent Tumor Suppression

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $443,116

## 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 (alpha, Beta, gamma, delta, epsilon, zeta) 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 ΔNp73. Thus, 
TAp73 and ΔNp73 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 ΔNp73 are prone to neurological defects. However, compared to TA and ΔN 
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:** 10330449
- **Project number:** 5R01CA081237-23
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Xinbin Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $443,116
- **Award type:** 5
- **Project period:** 1999-05-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10330449

## Citation

> US National Institutes of Health, RePORTER application 10330449, Mechanism of P73-dependent Tumor Suppression (5R01CA081237-23). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10330449. Licensed CC0.

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