A Genetic Screen Identifies TCF3/E2A and TRIAP1 as Pathway-Specific Regulators of the Cellular Response to p53 Activation

Zdenek Andrysik, Jihye Kim, Aik Choon Tan, Joaquín M. Espinosa

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)


The p53 transcription factor participates in diverse cellular responses to stress, including cell-cycle arrest, apoptosis, senescence, and autophagy. The molecular mechanisms defining the ultimate outcome of p53 activation remain poorly characterized. We performed a genome-wide genetic screen in human cells to identify pathway-specific coregulators of the p53 target gene CDKN1A (p21), an inhibitor of cell-cycle progression, versus BBC3 (PUMA), a key mediator of apoptosis. Our screen identified numerous factors whose depletion creates an imbalance in the p21:PUMA ratio upon p53 activation. The transcription factor TCF3, also known as E2A, drives p21 expression while repressing PUMA across cancer cell types of multiple origins. Accordingly, TCF3/E2A depletion impairs the cell-cycle-arrest response and promotes apoptosis upon p53 activation by chemotherapeutic agents. In contrast, TRIAP1 is a specific repressor of p21 whose depletion slows down cell-cycle progression. Our results reveal strategies for driving cells toward specific p53-dependent responses.

Original languageEnglish
Pages (from-to)1346-1354
Number of pages9
JournalCell Reports
Issue number5
Publication statusPublished - 2013 May 30

Bibliographical note

Funding Information:
We are grateful to all members of the Espinosa lab for invaluable discussion and reagents, in particular to Dr. Kelly Sullivan for preparing the HCT116 cells transduced with the shRNA library. This work was supported by NIH grant 5RO1CA117907-07 to J.M.E. and grants from the Cancer League of Colorado and Golfers Against Cancer/AMD Fund to A.C.T. J.M.E. is an HHMI Early Career Scientist. We thank Dr. Luis Fonrouge for inspiration.

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology


Dive into the research topics of 'A Genetic Screen Identifies TCF3/E2A and TRIAP1 as Pathway-Specific Regulators of the Cellular Response to p53 Activation'. Together they form a unique fingerprint.

Cite this