Nucleic Acids Research Advance Access published online on July 26, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn481
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Molecular Biology |
Cataloging and organizing p73 interactions in cell cycle arrest and apoptosis
lu11Polymer Research Center and Chemical Engineering Department, Bogazici University, Bebek-Istanbul 80815, Turkey, 2Basic Research Program, SAIC-Frederick, Inc., Center for Cancer Research Nanobiology Program, NCI-Frederick, Frederick, MD 21702, USA and 3Department of Human Genetics and Molecular Medicine, Sackler Institute of Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
*To whom correspondence should be addressed. Tel: +90 212 359 7002; Fax: +90 212 257 5032; Email: turkan{at}prc.boun.edu.tr
Correspondence may also be addressed to Ruth Nussinov. Tel: +1 301 846 5579; Fax: +1 301 846 5598; Email: ruthn{at}ncifcrf.gov
Received March 27, 2008. Revised July 7, 2008. Accepted July 10, 2008.
We have compiled the p73-mediated cell cycle arrest and apoptosis pathways. p73 is a member of the p53 family, consisting of p53, p63 and p73. p73 exists in several isoforms, presenting different domain structures. p73 functions not only as a tumor suppressor in apoptosis but also as differentiator in embryo development. p53 mutations are responsible for half of the human cancers; p73 can partially substitute mutant p53 as tumor suppressor. The pathways we assembled create a p73-centered network consisting of 53 proteins and 176 interactions. We clustered our network into five functional categories: Upregulation, Activation, Suppression, Transcriptional Activity and Degradation. Our literature searches led to discovering proteins (c-Jun and pRb) with apparent opposing functional effects; these indicate either currently missing proteins and interactions or experimental misidentification or functional annotation. For convenience, here we present the p73 network using the molecular interaction map (MIM) notation. The p73 MIM is unique amongst MIMs, since it further implements detailed domain features. We highlight shared pathways between p53 and p73. We expect that the compiled and organized network would be useful to p53 family-based studies.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors