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@article{Wang:2017:10.15252/embr.201642788,
author = {Wang, J and Okkeri, J and Pavic, K and Wang, Z and Kauko, O and Halonen, T and Sarek, G and Ojala, PM and Rao, Z and Xu, W and Westermarck, J},
doi = {10.15252/embr.201642788},
journal = {EMBO REPORTS},
pages = {437--450},
title = {Oncoprotein CIP2A is stabilized via interaction with tumor suppressor PP2A/B56},
url = {http://dx.doi.org/10.15252/embr.201642788},
volume = {18},
year = {2017}
}

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TY  - JOUR
AB  - Protein phosphatase 2A (PP2A) is a critical human tumor suppressor. Cancerous inhibitor of PP2A (CIP2A) supports the activity of several critical cancer drivers (Akt, MYC, E2F1) and promotes malignancy in most cancer types via PP2A inhibition. However, the 3D structure of CIP2A has not been solved, and it remains enigmatic how it interacts with PP2A. Here, we show by yeast twohybrid assays, and subsequent validation experiments, that CIP2A forms homodimers. The homodimerization of CIP2A is confirmed by solving the crystal structure of an Nterminal CIP2A fragment (amino acids 1–560) at 3.0 Å resolution, and by subsequent structurebased mutational analyses of the dimerization interface. We further describe that the CIP2A dimer interacts with the PP2A subunits B56α and B56γ. CIP2A binds to the B56 proteins via a conserved Nterminal region, and dimerization promotes B56 binding. Intriguingly, inhibition of either CIP2A dimerization or B56α/γ expression destabilizes CIP2A, indicating opportunities for controlled degradation. These results provide the first structure–function analysis of the interaction of CIP2A with PP2A/B56 and have direct implications for its targeting in cancer therapy.
AU  - Wang,J
AU  - Okkeri,J
AU  - Pavic,K
AU  - Wang,Z
AU  - Kauko,O
AU  - Halonen,T
AU  - Sarek,G
AU  - Ojala,PM
AU  - Rao,Z
AU  - Xu,W
AU  - Westermarck,J
DO  - 10.15252/embr.201642788
EP  - 450
PY  - 2017///
SN  - 1469-221X
SP  - 437
TI  - Oncoprotein CIP2A is stabilized via interaction with tumor suppressor PP2A/B56
T2  - EMBO REPORTS
UR  - http://dx.doi.org/10.15252/embr.201642788
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000395061000013&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/59371
VL  - 18
ER  -

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