The ASPP interaction network: electrostatic differentiation between pro- and anti-apoptotic proteins

Journal of Molecular Recognition : JMR
Hadar Benyamini, Assaf Friedler

Abstract

The ASPP proteins are apoptosis regulators: ASPP1 and ASPP2 promote, while iASPP inhibits, apoptosis. The mechanism by which these different outcomes are achieved is still unknown. The C-terminal ankyrin repeats and SH3 domain (ANK-SH3) mediate the interactions of the ASPP proteins with major apoptosis regulators such as p53, Bcl-2, and NFκB. The structure of the complex between ASPP2(ANK-SH3) and the core domain of p53 (p53CD) was previously determined. We have recently characterized the individual interactions of ASPP2(ANK-SH3) with Bcl-2 and NFκB, as well as a regulatory intramolecular interaction with the proline rich domain of ASPP2. Here we compared the ASPP interactions at two levels: ASPP2(ANK-SH3) with different proteins, and different ASPP family members with each protein partner. We found that the binding sites of ASPP2 to p53CD, Bcl-2, and NFκB are different, yet lie on the same face of ASPP2(ANK-SH3) . The intramolecular binding site to the proline rich domain overlaps the three intermolecular binding sites. To reveal the basis of functional diversity in the ASPP family, we compared their protein-binding domains. A subset of surface-exposed residues differentiates ASPP1 and ASPP2 from iASPP: ASPP1/2 are more negati...Continue Reading

References

Jul 25, 1976·Journal of Molecular Biology·C Chothia
Jun 21, 1994·Proceedings of the National Academy of Sciences of the United States of America·K IwabuchiS Fields
Jul 1, 1996·Molecular and Cellular Biology·L Naumovski, M L Cleary
Jan 1, 1996·Annual Review of Immunology·A S Baldwin
Sep 12, 1998·Science·J M Adams, S Cory
Feb 27, 1999·DNA Research : an International Journal for Rapid Publication of Reports on Genes and Genomes·T NagaseO Ohara
May 21, 1999·The Journal of Biological Chemistry·J P YangT Okamoto
Dec 1, 2000·Nature·B VogelsteinA J Levine
Mar 30, 2001·The Journal of Biological Chemistry·X Espanel, M Sudol
Oct 31, 2001·Molecular Cell·Y Samuels-LevX Lu
Jan 10, 2002·Proceedings of the National Academy of Sciences of the United States of America·Assaf FriedlerAlan R Fersht
Jan 14, 2003·Nature Genetics·Daniele BergamaschiXin Lu
Jun 26, 2003·Nucleic Acids Research·Torsten SchwedeManuel C Peitsch
Feb 27, 2004·Biochemical and Biophysical Research Communications·Yongheng CaoKuniyoshi Iwabuchi
Feb 17, 2005·Bioinformatics·Carlos J Camacho, Chao Zhang
Mar 4, 2005·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Shinya KobayashiTakashi Okamoto
Aug 5, 2006·The Journal of Biological Chemistry·Henning TidowAlan R Fersht
Jun 29, 2007·Proteins·Nelly AndrusierHaim J Wolfson
Oct 25, 2007·Biochemical Society Transactions·S RotemA Friedler
Jan 29, 2008·Protein and Peptide Letters·V AlvaR Sowdhamini
May 2, 2008·The Journal of Biological Chemistry·Shahar RotemAssaf Friedler
Aug 23, 2008·Proceedings of the National Academy of Sciences of the United States of America·Chen KatzAssaf Friedler
Feb 28, 2009·The Journal of Biological Chemistry·Jinwoo AhnAngela M Gronenborn

❮ Previous
Next ❯

Citations

Dec 13, 2012·Biochimica Et Biophysica Acta·Haidar Akl, Geert Bultynck
Sep 8, 2012·Cellular and Molecular Life Sciences : CMLS·Giovanni MonacoGeert Bultynck
Feb 19, 2019·Chemical Science·Anat Iosub-AmirRachel Nechushtai

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis