p73α1, a p73 C-terminal isoform, regulates tumor suppression and the inflammatory response via Notch1

Kyra Nicole Laubach, Wensheng Yan, Xiangmudong Kong, Wenqiang Sun, Mingyi Chen, Jin Zhang, Xinbin Chen

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


p73, a p53 family member, undergoes alternative splicing at the 30 end to produce multiple isoforms, but their expression and activity are largely unknown. Thus, CRISPR was used to knock out exon 12 (E12) in human cancer cell lines and mice, leading to isoform switch from p73α to isoform p73α1. We found that p73α1 is naturally expressed and induced by DNA damage. We also found that knockout of E12 suppresses cell growth and migration in H1299 and MIA PaCa-2 cells and promotes cellular senescence in mouse embryonic fibroblasts. Similarly, ectopic expression of p73α1 suppresses cell proliferation, whereas knockdown of p73α1 restores the cell proliferative and migratory capacities of E122/2 cells. Consistently, we found that E12+/2 mice are not prone to spontaneous tumors. Instead, E12+/2 mice are prone to systemic inflammation and exhibit elevated TNFα expression in inflamed tissues. Moreover, we found that Notch1, a master regulator of the inflammatory response, is regulated by p73α1 and highly expressed in E122/2 cells and inflamed E12+/2 mouse tissues. Furthermore, through knockdown of p73α1 and/or Notch1 in E122/2 cells, we found that Notch1 is necessary for p73α1-mediated growth suppression. Together, these data suggest that p73α1 plays a critical role in tumor suppression and the inflammatory response via Notch1.

Original languageEnglish (US)
Article numbere2123202119
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number22
StatePublished - May 31 2022


  • Notch1 pathway
  • p53 family
  • p73
  • p73 C-terminal isoforms
  • tumor suppressor

ASJC Scopus subject areas

  • General


Dive into the research topics of 'p73α1, a p73 C-terminal isoform, regulates tumor suppression and the inflammatory response via Notch1'. Together they form a unique fingerprint.

Cite this