p53-family proteins and their regulators: hubs and spokes in tumor suppression

Abstract

The tumor suppressor p53 is a central hub in a molecular network controlling cell proliferation and death in response to potentially oncogenic conditions, and a wide array of covalent modifications and protein interactions modulate the nuclear and cytoplasmic activities of p53. The p53 relatives, p73 and p63, are entangled in the same regulatory network, being subject at least in part to the same modifications and interactions that convey signals on p53, and actively contributing to the resulting cellular output. The emerging picture is that of an interconnected pathway, in which all p53-family proteins are involved in the response to oncogenic stress and physiological inputs. Therefore, common and specific interactors of p53-family proteins can have a wide effect on function and dysfunction of this pathway. Many years of research have uncovered an impressive number of p53-interacting proteins, but much less is known about protein interactions of p63 and p73. Yet, many interactors may be shared by multiple p53-family proteins, with similar or different effects. In this study we review shared interactors of p53-family proteins with the aim to encourage research into this field; this knowledge promises to unveil regulatory elements that could be targeted by a new generation of molecules, and allow more efficient use of currently available drugs for cancer treatment.

Aggregation and Prion-Like Properties of Misfolded Tumor Suppressors: Is Cancer a Prion Disease?

“…Similar to p53, family members include transcription factors involved in the regulation of the cell cycle, proliferation, differentiation, DNA damage response, and apoptosis Collavin et al 2010). p63 and p73 not only bind to and activate consensus p53 response elements, such as p21 and Puma, but also have unique gene targets Osada et al 2005).…”

TAp73 is downregulated in oocytes from women of advanced reproductive age

“…25 In this study, we analyzed by RT-PCR Real Time 16 MII oocytes, 10 from women younger than 35 y of age disorders. 11,12 Female reproductive aging is the process dictated by a gradual decrease in both the quantity and the quality of the oocytes. The pool of ovarian follicles is progressively reduced during female reproductive lifespan, which ends with menopause at a mean age of 50-51 y.…”

Interaction between p53 and estradiol pathways in transcriptional responses to chemotherapeutics

“…p53 activators can vary in their impact on p53 post-translational modifications and alter transcriptome responses. 58,59 It is important to note that, while p53 has been implicated, there may be other reasons for the genotoxic stress/ER synergistic responses.…”