ASPP proteins discriminate between PP1 catalytic subunits through their SH3 domain and the PP1 C-tail
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Author
Bertran, M TeresaMouilleron, Stéphane
Zhou, Yanxiang
Bajaj, Rakhi
Uliana, Federico
Kumar, Ganesan Senthil
van Drogen, Audrey
Lee, Rebecca
Banerjee, Jennifer J
Hauri, Simon
O'Reilly, Nicola
Gstaiger, Matthias
Page, Rebecca
Peti, Wolfgang
Tapon, Nicolas
Affiliation
Univ Arizona, Dept Chem & BiochemIssue Date
2019-02-15
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NATURE PUBLISHING GROUPCitation
Bertran, M. T., Mouilleron, S., Zhou, Y., Bajaj, R., Uliana, F., Kumar, G. S., ... & O’Reilly, N. (2019). ASPP proteins discriminate between PP1 catalytic subunits through their SH3 domain and the PP1 C-tail. Nature communications, 10(1), 771.Journal
NATURE COMMUNICATIONSRights
© The Author(s) 2019.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
Serine/threonine phosphatases such as PP1 lack substrate specificity and associate with a large array of targeting subunits to achieve the requisite selectivity. The tumour suppressor ASPP (apoptosis-stimulating protein of p53) proteins associate with PP1 catalytic subunits and are implicated in multiple functions from transcriptional regulation to cell junction remodelling. Here we show that Drosophila ASPP is part of a multiprotein PP1 complex and that PP1 association is necessary for several in vivo functions of Drosophila ASPP. We solve the crystal structure of the human ASPP2/PP1 complex and show that ASPP2 recruits PP1 using both its canonical RVxF motif, which binds the PP1 catalytic domain, and its SH3 domain, which engages the PP1 C-terminal tail. The ASPP2 SH3 domain can discriminate between PP1 isoforms using an acidic specificity pocket in the n-Src domain, providing an exquisite mechanism where multiple motifs are used combinatorially to tune binding affinity to PP1.Note
Open access journalISSN
2041-1723PubMed ID
30770806Version
Final published versionSponsors
Francis Crick Institute; Cancer Research UK [FC001175]; UK Medical Research Council [FC001175]; Wellcome Trust [FC001175, 107885/Z/15/Z]; NIH [R01-GM098482, R01-NS091336]; European Union 7th Framework Programme SYBILLA (Systems Biology of T-Cell Activation); Innovative Medicines Initiative project ULTRA-DD [115766]Additional Links
https://www.nature.com/articles/s41467-019-08686-0ae974a485f413a2113503eed53cd6c53
10.1038/s41467-019-08686-0
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