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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Identification of Akt interaction protein PHF20/TZP that transcriptionally regulates p53
Sungman Park1, Donghwa Kim, Han C Dan
1Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
Abstract:
Akt regulates a diverse array of cellular functions, including cell survival, proliferation, differentiation, and metabolism. Although a number of molecules have been identified as upstream regulators and downstream targets of Akt, the mechanisms by which Akt regulates these cellular processes remain elusive. Here, we demonstrate that a novel transcription factor, PHF20/TZP (referring to Tudor and zinc finger domain containing protein), binds to Akt and induces p53 expression at the transcription level. Knockdown of PHF20 significantly reduces p53. PHF20 inhibits cell growth, DNA synthesis, and cell survival. Akt phosphorylates PHF20 at Ser(291) in vitro and in vivo, which results in its translocation from the nucleus to the cytoplasm and attenuation of PHF20 function. These data indicate that PHF20 is a substrate of Akt and plays a role in Akt cell survival/growth signaling.
Insights
A novel protein, PHF20, regulates p53 and cell growth. Akt phosphorylates PHF20, inhibiting its function and promoting cell survival signaling.
Area of Science:
- Molecular Biology
- Cellular Signaling
Background:
- Akt signaling pathway regulates crucial cellular functions like survival, proliferation, differentiation, and metabolism.
- The precise mechanisms underlying Akt's regulation of these cellular processes are not fully understood.
Purpose of the Study:
- To investigate the role of the novel transcription factor PHF20/TZP in Akt signaling.
- To elucidate the interaction between PHF20 and Akt and its impact on cellular processes.
Main Methods:
- Investigated the interaction between PHF20 and Akt using in vitro and in vivo assays.
- Assessed the effect of PHF20 knockdown on p53 expression.
- Examined the impact of Akt phosphorylation on PHF20 localization and function.
Main Results:
- PHF20 binds to Akt and transcriptionally induces p53 expression.
- Knockdown of PHF20 leads to a significant reduction in p53 levels.
- PHF20 inhibits cell growth, DNA synthesis, and cell survival.
- Akt phosphorylates PHF20 at Ser(291), causing its translocation from the nucleus to the cytoplasm and reducing its inhibitory function.
Conclusions:
- PHF20 is a novel substrate of Akt.
- PHF20 plays a role in Akt-mediated cell survival and growth signaling.
- Akt-mediated phosphorylation of PHF20 is a key regulatory mechanism in this pathway.
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