title: TP63 and TP73 in cancer, an unresolved "family" puzzle of complexity, redundancy and hierarchy.
abstract: TP53 belongs to a small gene family that includes, in mammals, two additional paralogs, TP63 and TP73. The p63 and p73 proteins are structurally and functionally similar to p53 and their activity as transcription factors is regulated by a wide repertoire of shared and unique post-translational modifications and interactions with regulatory cofactors. p63 and p73 have important functions in embryonic development and differentiation but are also involved in tumor suppression. The biology of p63 and p73 is complex since both TP63 and TP73 genes are transcribed into a variety of different isoforms that give rise to proteins with antagonistic properties, the TA-isoforms that act as tumor-suppressors and DN-isoforms that behave as proto-oncogenes. The p53 family as a whole behaves as a signaling "network" that integrates developmental, metabolic and stress signals to control cell metabolism, differentiation, longevity, proliferation and death. Despite the progress of our knowledge, the unresolved puzzle of complexity, redundancy and hierarchy in the p53 family continues to represent a formidable challenge.
authors.affiliation: Dermatology Unit, Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Costanzo
authors.affiliation: Laboratory of Molecular Oncology, Department of Molecular Medicine, Sapienza University of Rome, Italy; Center for Life Nanosciences (CNLS) - IIT/Sapienza, Rome, Italy.
authors.forename: Natalia
authors.initials: N
authors.lastname: Pediconi
authors.affiliation: Dermatology Unit, Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Narcisi
authors.affiliation: Center for Life Nanosciences (CNLS) - IIT/Sapienza, Rome, Italy; Laboratory of Gene Expression, Department of Internal Medicine (DMISM), Sapienza University of Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Guerrieri
authors.affiliation: Center for Life Nanosciences (CNLS) - IIT/Sapienza, Rome, Italy; Laboratory of Gene Expression, Department of Internal Medicine (DMISM), Sapienza University of Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Belloni
authors.affiliation: Dermatology Unit, Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fausti
authors.affiliation: Dermatology Unit, Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Botti
authors.affiliation: Center for Life Nanosciences (CNLS) - IIT/Sapienza, Rome, Italy; Laboratory of Gene Expression, Department of Internal Medicine (DMISM), Sapienza University of Rome, Italy. Electronic address: massimo.levrero@uniroma1.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Levrero
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C115051:TP63 protein, human; C000606460:TP73 protein, human; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins
keywords: Development; TP53; TP63; TP73; Tumor suppressors