5UFL

Crystal structure of a CIP2A core domain

5UFL の概要

• エントリーDOI: 10.2210/pdb5ufl/pdb
• 分子名称: Protein CIP2A, ZINC ION (2 entities in total)
• 機能のキーワード: cip2a, pp2a, signaling protein
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Membrane ; Single-pass membrane protein : Q8TCG1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 124715.67

構造登録者

Wang, Z.,Wang, J.,Rao, Z.,Xu, W. (登録日: 2017-01-04, 公開日: 2017-02-15, 最終更新日: 2024-03-06)

主引用文献

Wang, J.,Okkeri, J.,Pavic, K.,Wang, Z.,Kauko, O.,Halonen, T.,Sarek, G.,Ojala, P.M.,Rao, Z.,Xu, W.,Westermarck, J.
Oncoprotein CIP2A is stabilized via interaction with tumor suppressor PP2A/B56.
EMBO Rep., 18:437-450, 2017

PubMed Abstract: 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 two-hybrid assays, and subsequent validation experiments, that CIP2A forms homodimers. The homodimerization of CIP2A is confirmed by solving the crystal structure of an N-terminal CIP2A fragment (amino acids 1-560) at 3.0 Å resolution, and by subsequent structure-based 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 N-terminal 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.

PubMed: 28174209
DOI: 10.15252/embr.201642788

実験手法

X-RAY DIFFRACTION (3 Å)