2L9M

Structure of cIAP1 CARD

2L9M の概要

• エントリーDOI: 10.2210/pdb2l9m/pdb
• NMR情報: BMRB: 17478
• 分子名称: Baculoviral IAP repeat-containing protein 2 (1 entity in total)
• 機能のキーワード: card, iap, caspase, apoptosis inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm (Potential): Q13490
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15147.40

構造登録者

Day, C.L.,Rautureau, G.J.P.,Hinds, M.G. (登録日: 2011-02-21, 公開日: 2011-08-17, 最終更新日: 2024-05-15)

主引用文献

Lopez, J.,John, S.W.,Tenev, T.,Rautureau, G.J.,Hinds, M.G.,Francalanci, F.,Wilson, R.,Broemer, M.,Santoro, M.M.,Day, C.L.,Meier, P.
CARD-mediated autoinhibition of cIAP1's E3 ligase activity suppresses cell proliferation and migration.
Mol.Cell, 42:569-583, 2011

PubMed Abstract: E3 ligases mediate the covalent attachment of ubiquitin to target proteins thereby enabling ubiquitin-dependent signaling. Unraveling how E3 ligases are regulated is important because miscontrolled ubiquitylation can lead to disease. Cellular inhibitor of apoptosis (cIAP) proteins are E3 ligases that modulate diverse biological processes such as cell survival, proliferation, and migration. Here, we have solved the structure of the caspase recruitment domain (CARD) of cIAP1 and identified that it is required for cIAP1 autoregulation. We demonstrate that the CARD inhibits activation of cIAP1's E3 activity by preventing RING dimerization, E2 binding, and E2 activation. Moreover, we show that the CARD is required to suppress cell proliferation and migration. Further, CARD-mediated autoregulation is also necessary to maximally suppress caspase-8-dependent apoptosis and vascular tree degeneration in vivo. Taken together, our data reveal mechanisms by which the E3 ligase activity of cIAP1 is controlled, and how its deregulation impacts on cell proliferation, migration and cell survival.

PubMed: 21549626
DOI: 10.1016/j.molcel.2011.04.008

実験手法

SOLUTION NMR