TAB2 and TAB3 Activate the NF-κB Pathway through Binding to Polyubiquitin Chains

Essential roles of K63-linked polyubiquitin-binding proteins TAB2 and TAB3 in B cell activation via MAPKs.

Polyubiquitination of proteins plays a critical role in the activation of immune cells. K63-linked polyubiquitin-binding proteins TGF-β-activated kinase 1 (TAK1)-binding protein (TAB)2 and TAB3 are implicated in NF-κB signaling via TAK1 activation. However, TAB2 alone is dispensable for NF-κB activation in embryonic fibroblasts, and the functional roles of TAB2 and TAB3 in immune cells has yet ...

NF-κB signaling: Flipping the Switch with Polyubiquitin Chains

Cells respond rapidly to changes in their internal and external environments, often by using post-translational protein modifications to transmit signals from the cell surface or internal sites to the nucleus. These signaling pathways allow cells to respond to growth signals, tolerate stresses or trigger programmed cell death. In general, signaling pathway activation is transient, with feedback...

Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by NZF domains of TAB2 and TAB3.

TAB2 and TAB3 activate the Jun N-terminal kinase and nuclear factor-kappaB pathways through the specific recognition of Lys 63-linked polyubiquitin chains by its Npl4 zinc-finger (NZF) domain. Here we report crystal structures of the TAB2 and TAB3 NZF domains in complex with Lys 63-linked diubiquitin at 1.18 and 1.40 A resolutions, respectively. Both NZF domains bind to the distal ubiquitin thr...

TAB3 in B Cell Activation via MAPKs Polyubiquitin-Binding Proteins TAB2 and Essential Roles of K63-Linked

Inhibition of autophagy by TAB2 and TAB3.

Autophagic responses are coupled to the activation of the inhibitor of NF-κB kinase (IKK). Here, we report that the essential autophagy mediator Beclin 1 and TGFβ-activated kinase 1 (TAK1)-binding proteins 2 and 3 (TAB2 and TAB3), two upstream activators of the TAK1-IKK signalling axis, constitutively interact with each other via their coiled-coil domains (CCDs). Upon autophagy induction, TAB2 ...