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. 2010:2010:283863.
doi: 10.1155/2010/283863. Epub 2011 Jan 13.

p73-Binding Partners and Their Functional Significance

Toshinori Ozaki  1 , Natsumi Kubo, Akira Nakagawara
Affiliations

p73-Binding Partners and Their Functional Significance

Toshinori Ozaki et al. Int J Proteomics. 2010.

Abstract

p73 is one of the tumor-suppressor p53 family of nuclear transcription factor. As expected from the structural similarity between p53 and p73, p73 has a tumor-suppressive function. However, p73 was rarely mutated in human primary tumors. Under normal physiological conditions, p73 is kept at an extremely low level to allow cells normal growth. In response to a certain subset of DNA damages, p73 is induced dramatically and transactivates an overlapping set of p53-target genes implicated in the promotion of cell cycle arrest and/or apoptotic cell death. Cells undergo cell cycle arrest and/or apoptotic cell death depending on the type and strength of DNA damages. p73 is regulated largely through the posttranslational modifications such as phosphorylation and acetylation. These chemical modifications are tightly linked to direct protein-protein interactions. In the present paper, the authors describe the functional significance of the protein-protein interactions in the regulation of proapoptotic p73.

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Figures

Figure 1
Figure 1
Dominant-negative effect of ΔNp73 on wild-type p73. In response to DNA damage, wild-type p73 transactivates its dominant-negative inhibitor ΔNp73. The intracellular balance between the expression levels of wild-type p73 and ΔNp73 is a critical determinant of cell fate.
Figure 2
Figure 2
p73-dependent apoptotic cell death in response to DNA damage. Upon DNA damage, phospho-ATM phosphorylates IKK-α and promotes nuclear accumulation of IKK-α. IKK-α then enhances transcriptional as well as proapoptotic function of p73 in a p53-independent manner.
Figure 3
Figure 3
p73/ASPP complex preferentially induces the expression of proapoptotic BAX and PUMA. p73 forms a complex with ASPP1 or with ASPP2, and these transcriptional complexes selectively transactivate proapoptotic p73-target genes such as BAX and PUMA.
Figure 4
Figure 4
Dominant-negative behavior of mutant p53 toward wild-type p73 and p53. Mutant form of p53 binds to wild-type p73 as well as p53 and strongly inhibits their tumor suppressive function.
See this image and copyright information in PMC

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