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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
From Genome Guardian to Immune Modulator: The Expanding Roles of Tumor Suppressor p53
Weiwei Wang1, Juan Liu1, Zhaohui Feng1
1Department of Radiation Oncology, Rutgers Cancer Institute, Rutgers-The State University of New Jersey, New Brunswick, New Jersey, USA.
Abstract:
p53 is a key tumor suppressor, and mutations in the p53 gene occur in more than half of all human cancers. p53, which is under tight and complex regulation in cells, functions primarily as a transcription factor regulating genes involved in many cellular processes, including cell cycle arrest, apoptosis, senescence, ferroptosis, and metabolism, thereby maintaining genomic integrity and preventing tumorigenesis. While the cell-intrinsic functions of p53, which contribute to its tumor-suppressive activity, have been extensively studied, it is now clear that p53 also plays an important role in immune regulation, a connection first observed when p53 was identified as a cellular protein interacting with viral antigens. Growing evidence shows that p53 modulates both innate and adaptive immunity by regulating cytokine production, antigen presentation, and the functions of immune cells, thereby contributing to host defense against infections, inflammatory responses, and antitumor immunity. In this review, we summarize and discuss the multifaceted roles of p53 and its signaling in regulating immune functions and their implications in human diseases, particularly cancer. A better understanding of the immune-related functions of p53 is crucial for advancing cancer treatment and broadening insights into immunity and disease.
Insights
The p53 protein is a crucial tumor suppressor that also regulates immune responses. Understanding its multifaceted roles in immunity is vital for developing new cancer treatments and advancing our knowledge of disease.
Area of Science:
- Molecular Biology
- Immunology
- Oncology
Background:
- The p53 protein is a critical tumor suppressor, with mutations found in over half of human cancers.
- p53 acts as a transcription factor, regulating genes involved in cell cycle arrest, apoptosis, senescence, ferroptosis, and metabolism to maintain genomic stability.
- While its cell-intrinsic tumor-suppressive functions are well-studied, p53 also significantly impacts immune regulation.
Purpose of the Study:
- To review the multifaceted roles of p53 signaling in regulating immune functions.
- To discuss the implications of p53's immune-related functions in human diseases, especially cancer.
Main Methods:
- This review synthesizes existing research on p53's involvement in immunity.
- The analysis focuses on how p53 modulates innate and adaptive immune responses.
Main Results:
- p53 plays a key role in host defense against infections and inflammatory responses.
- p53 influences antitumor immunity by regulating cytokine production, antigen presentation, and immune cell functions.
- Evidence indicates p53's interaction with viral antigens highlights its immune regulatory connection.
Conclusions:
- p53 is a crucial regulator of both intrinsic cellular processes and immune responses.
- A comprehensive understanding of p53's immune functions is essential for advancing cancer therapy and immunological insights.
- Further research into p53's immune roles promises to broaden our understanding of immunity and disease pathogenesis.
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