2005-2008 Publications

Highlights
* = co-first author, † = corresponding author

XIAP induces NF-κB activation via the BIR1/TAB1 interaction and BIR1 dimerization.

Lu M, Lin SC, Huang Y, Kang Y, Rich R, Lo YC, Myszka D, Han J, Wu H. Mol Cell (2007). PDF

In addition to caspase inhibition, X-linked inhibitor of apoptosis (XIAP) induces NF-κB and MAP kinase activation during TGF-b and BMP receptor signaling and upon overexpression. Here we show that the BIR1 domain of XIAP, which has no previously ascribed function, directly interacts with TAB1 to induce NF-kappaB activation. TAB1 is an upstream adaptor for the activation of the kinase TAK1... Read More

Death Domain Assembly Mechanism Revealed by Crystal Structure of the Oligomeric PIDDosome Core Complex

Park H, Logette E, Rauser S, Cuenin S, Walz T, Tschopp J, Wu H. Cell (2007). PDF

Proteins of the death domain (DD) superfamily mediate assembly of oligomeric signaling complexes for the activation of caspases and kinases via unknown mechanisms. Here we report the crystal structure of the PIDD DD and RAIDD DD complex, which forms the core of the caspase-2-activating complex PIDDosome. Although RAIDD DD and PIDD DD are monomers, they assemble into a complex that comprises seven... Read More

Caspase-9 Holoenzyme Is a Specific and Optimal Procaspase-3 Processing Machine.

Yin Q, Park H, Chung J, Lin SC, Lo YC, Graca L, Jiang X, Wu H. Mol Cell (2006). PDF

Caspase-9 activation is critical for intrinsic cell death. The activity of caspase-9 is increased dramatically
upon association with the apoptosome, and the apoptosome bound caspase-9 is the caspase-9 holoenzyme
(C9Holo). In this study, we use quantitative enzymatic assays to fully characterize C9Holo and a leucine-zipper-linked dimeric caspase-9 (LZ-C9). We surprisingly show that LZ-C9 is... Read More

Crystal Structure of MC159 Reveals Molecular Mechanism of DISC Assembly and FLIP Inhibition

Yang J K*, Wang L*, Zheng L, Wan F, Ahmed M, Lenardo M, Wu HMol Cell (2005). PDF

Death receptors (DRs) in the Tumor Necrosis Factor (TNF) Receptor (TNFR) superfamily mediate the extrinsic pathway of apoptosis and play critical roles in embryonic development, cellular homeostasis, and immune regulation (French and Tschopp, 2003; Locksley et al., 2001; Peter and Krammer, 2003; Wajant, 2002). Current members of the DR subfamily include Fas (also known as CD95 and APO-1), TNF-R1... Read More

Bicarbonate activation of adenylyl cyclases via promotion of the catalytic cycle: active site closure and metal recruitment

Steegborn C, Litvin T N, Levin L R, Buck J, Wu H. Nature Struct. & Mol. Biol. (2005). PDF | Commentary

The ubiquitous second messenger cAMP regulates a large variety of essential physiological processes such as gene expression, chromosome segregation and cellular metabolism. In mammalian cells, cAMP is synthesized by a family of nine transmembrane adenylyl cyclases (tmACs) and one sAC1. Unlike tmACs, which localize to the cellular membrane and respond to extracellular stimuli via... Read More

Other Publications (2005-2008)
* = co-first author, † = corresponding author

Lin SC*, Chung JY*, Lamothe B, Rajashankar K, Lu M, Lo YC, Lam AY, Darnay BG, Wu H. (2008). Molecular Basis for the Unique Deubiquitinating Activity of the NF-kappaB Inhibitor A20. J Mol Biol. 376:526-40. Commentary

Lo YC*, Maddineni U*, Chung JY, Rich RL, Myszka DG, Wu H†. (2008). High-affinity interaction between IKKbeta and NEMO. Biochemistry. 47:3109-16

Wu H, Tschopp J, Lin SC. (2007). Smac mimetics and TNFalpha: a dangerous liaison? Cell. 131:655-65

Lin SC, Huang Y, Lo YC, Lu M, Wu H. (2007). Crystal Structure of the BIR1 Domain of XIAP in Two Crystal Forms. J Mol Biol. 372:847-854

Gao Z, Tian Y, Wang J, Yin Q, Wu H, Li YM, Jiang X. (2007). A dimeric Smac/diablo peptide directly relieves caspase-3 inhibition by XIAP: Dynamic and cooperative regulation of XIAP by Smac/Diablo. J Biol Chem. 282:30718-27

Park H, Wu, H. (2007). Crystallization and preliminary X-ray crystallographic studies of the oligomeric death domain complex between PIDD and RAIDD. Acta Crystallogr. F63:229-32

Besse A, Lamothe B, Campos A, Webster W, Maddineni U, Lin SC, Wu, H, Darnay B. (2007). TAK1-dependent signaling requires functional interaction with TAB2/TAB3. J Biol Chem. 282:3918-28

Lamothe B, Besse A, Campos AD, Webster WK, Wu H and Darnay BG. (2007). Site-specific Lys63-linked TRAF6 auto-ubiquitination is a critical determinant of IKK activation. J Biol Chem. 282:4102-12

Yan S, Chen X, Wu H. (2007). ABAD: Mitochondrial Target for A!-Mediated Cellular Perturbation in Alzheimer Disease. in Research Progress in Alzheimer's Disease and Dementia, Vol. 3, edited by Miao-Kun Sun. pages 175-189

Park H, Lo YC, Lin SC, Wang L, Yang J, Wu H. (2007). The Death Domain Superfamily in Intracellular Signaling of Apoptosis and Inflammation. Ann Rev Immunol. 25:561-86

Lu M, Min T, Eliezer D, Wu H. (2006). A novel role for native chemical ligation in covalent caspase inhibition by p35Chemistry and Biology. 13: 117-22. Commentary

Park H H, Tookes H E, Wu H. (2006). Crystallization and preliminary X-ray crystallographic studies of Drep-3, a DFF-related protein from Drosophila melanogaster. Acta Crystallogr. F62:597-599

Muppidi J, Lobito A, Yang J K, Wang L, Wu H, Siegel R. (2006). Homotypic FADD interactions though a conserved RXDLL motif are required for death receptor-induced apoptosisCell death and differentiation. 13:1641-50

Guasparri I, Wu H, Cesarman E. (2006). The KSHV oncoprotein vFLIP contains a TRAF-interacting motif and requires TRAF2 and TRAF3 for signalingEMBO Rep. 7:114-9

Park H H, Wu H. (2006). Crystal Structure of RAIDD Death Domain Implicates Potential Mechanism of PIDDosome Assembly. J Mol Biol. 357:358-64

Chung J, Lu M, Yin Q, Lin SC, Wu H. (2006). Molecular basis for the unique specificity of TRAF6. In TNF Receptor Associated Factors, edited by Hao Wu, Pages 122-130

Chung J, Lu M, Yin Q, Wu H. (2006). Structural revelation of TRAF2 function. In TNF Receptor Associated Factors, edited by Hao Wu. Pages 93-113

Steegborn C*, Litvin TN*, Hess KC, Capper AB, Taussig R, Buck J, Levin LR, Wu H (2005). A novel mechanism for adenylyl cyclase inhibition from the crystal structure of its complex with catechol estrogen. J Biol Chem. 280:31754-93