Differential regulation of transcription and induction of programmed cell death by human p53-family members p63 and p73.

FEBS Lett

Medizinische Klinik und Poliklinik II, Max Bürger Forschungszentrum, Universität Leipzig, Johannisallee 30, D-04103, Leipzig, Germany.

Published: August 2002

The p53 tumor suppressor acts as a transcription factor and has a central function in controlling apoptosis. With p63 and p73 two genes coding for proteins homologous to p53 have been identified. We describe the properties of seven human p63 and p73 proteins as transcriptional activators of p21WAF1/CIP1 expression and apoptotic inducers in direct comparison to p53 in the same assay systems employing DLD-1-tet-off colon cells. Programmed cell death is detected in cells expressing high levels of p53 and p73alpha. Cells overexpressing TAp63alpha, TAp63gamma, TA*p63alpha, TA*p63gamma, DeltaNp63alpha, and DeltaNp63gamma display low or no detectable apoptosis.

Download full-text PDF

Source
http://dx.doi.org/10.1016/s0014-5793(02)03093-4DOI Listing

Publication Analysis

Top Keywords

p63 p73
12
programmed cell
8
cell death
8
differential regulation
4
regulation transcription
4
transcription induction
4
induction programmed
4
death human
4
human p53-family
4
p53-family members
4

Similar Publications

The mechanism by which DNA-damage affects self-renewal and pluripotency remains unclear. DNA damage and repair mechanisms have been largely elucidated in mutated cancer cells or simple eukaryotes, making valid interpretations on early development difficult. Here we show the impact of ionizing irradiation on the maintenance and early differentiation of mouse embryonic stem cells (ESCs).

View Article and Find Full Text PDF

BRD4 sustains p63 transcriptional program in keratinocytes.

Biol Direct

November 2024

Department of Experimental Medicine, TOR, University of Rome "Tor Vergata", 00133, Rome, Italy.

Here, we investigated the potential interaction between bromodomain-containing protein 4 (BRD4), an established epigenetic modulator and transcriptional coactivator, and p63, a member of the p53 transcription factor family, essential for epithelial development and skin homeostasis. Our protein-protein interaction assays demonstrated a strong and conserved physical interaction between BRD4 and the p53 family members-p63, p73, and p53-suggesting a shared binding region among these proteins. While the role of BRD4 in cancer development through its interaction with p53 has been explored, the effects of BRD4 and Bromodomain and Extra Terminal (BET) inhibitors in non-transformed cells, such as keratinocytes, remain largely unknown.

View Article and Find Full Text PDF

Crosstalk between paralogs and isoforms influences p63-dependent regulatory element activity.

Nucleic Acids Res

December 2024

Department of Biological Sciences and The RNA Institute, University at Albany, State University of New York, 1400 Washington Ave, Albany, NY 12222, USA.

The p53 family of transcription factors (p53, p63 and p73) regulate diverse organismal processes including tumor suppression, maintenance of genome integrity and the development of skin and limbs. Crosstalk between transcription factors with highly similar DNA binding profiles, like those in the p53 family, can dramatically alter gene regulation. While p53 is primarily associated with transcriptional activation, p63 mediates both activation and repression.

View Article and Find Full Text PDF

Oncogenic p53 triggers amyloid aggregation of p63 and p73 liquid droplets.

Commun Chem

September 2024

Institute of Medical Biochemistry Leopoldo de Meis, National Institute of Science and Technology for Structural Biology and Bioimaging, National Center of Nuclear Magnetic Resonance Jiri Jonas, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

P53 Phase separation is crucial towards amyloid aggregation and p63 and p73 have enhanced expression in tumors. This study examines the phase behaviors of p53, p63, and p73. Here we show that unlike the DNA-binding domain of p53 (p53C), the p63C and p73C undergo phase separation, but do not form amyloids under physiological temperatures.

View Article and Find Full Text PDF

Understanding the complexity of p53 in a new era of tumor suppression.

Cancer Cell

June 2024

Institute for Cancer Genetics, and Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA; Department of Pathology and Cell Biology, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA. Electronic address:

p53 was discovered 45 years ago as an SV40 large T antigen binding protein, coded by the most frequently mutated TP53 gene in human cancers. As a transcription factor, p53 is tightly regulated by a rich network of post-translational modifications to execute its diverse functions in tumor suppression. Although early studies established p53-mediated cell-cycle arrest, apoptosis, and senescence as the classic barriers in cancer development, a growing number of new functions of p53 have been discovered and the scope of p53-mediated anti-tumor activity is largely expanded.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!