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| Status |
Public on May 07, 2024 |
| Title |
Dichotomous transactivation domains contribute to growth inhibitory and promotion functions of TAp73 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The transcription factor p73, a member of the p53 tumor-suppressor family, regulates cell death and also supports tumorigenesis, though the mechanistic basis for the dichotomous functions is poorly understood. We report here the identification of an alternate transactivation domain (TAD) located at the extreme carboxyl (C)-terminus of TAp73β, a commonly expressed p73 isoform. Mutational disruption of this TAD significantly reduced TAp73β’s transactivation activity, to a level observed when the amino (N)-TAD that is similar to p53’s TAD is mutated. Mutation of both TADs almost completely abolished TAp73β’s transactivation activity. Expression profiling highlighted a unique set of targets involved in extracellular matrix-receptor interaction and focal adhesion to be regulated by the C-TAD, resulting in FAK phosphorylation, distinct from the N-TAD targets that are common to p53 and involved in growth inhibition. Interestingly, the C-TAD targets are also regulated by the oncogenic, amino-terminal deficient DNp73β isoform. Consistently, mutation of C-TAD reduces cellular migration and proliferation. Mechanistically, selective binding of TAp73β to DNAJA1 is required for the transactivation of C-TAD target genes, and silencing DNAJA1 expression abrogated all C-TAD-mediated effects. Taken together, our results provide a mechanistic basis for the dichotomous functions of TAp73 in the regulation cellular growth through its distinct TADs.
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| Overall design |
Microarray analysis was performed on 17 samples using [Clariom_S_Human] Affymetrix Clariom S Assay, Human (GPL23159).
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| Contributor(s) |
Li D, Sabapathy K |
| Citation missing |
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| Submission date |
Mar 22, 2024 |
| Last update date |
May 07, 2024 |
| Contact name |
Kanaga Sabapathy |
| E-mail(s) |
kanaga.sabapathy@ntu.edu.sg
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| Organization name |
Nanyang Technological University Singapore
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| Department |
SBS
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| Street address |
60 Nanyang Drive
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| City |
Singapore |
| State/province |
Singapore |
| ZIP/Postal code |
637551 |
| Country |
Singapore |
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| Platforms (1) |
| GPL23159 |
[Clariom_S_Human] Affymetrix Clariom S Assay, Human (Includes Pico Assay) |
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| Samples (17)
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| Relations |
| BioProject |
PRJNA1090954 |
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