Abstract:
:The activation of NF-kappaB and IKK requires an upstream kinase complex consisting of TAK1 and adaptor proteins such as TAB1, TAB2, or TAB3. TAK1 is in turn activated by TRAF6, a RING domain ubiquitin ligase that facilitates the synthesis of lysine 63-linked polyubiquitin chains. Here we present evidence that TAB2 and TAB3 are receptors that bind preferentially to lysine 63-linked polyubiquitin chains through a highly conserved zinc finger (ZnF) domain. Mutations of the ZnF domain abolish the ability of TAB2 and TAB3 to bind polyubiquitin chains, as well as their ability to activate TAK1 and IKK. Significantly, replacement of the ZnF domain with a heterologous ubiquitin binding domain restored the ability of TAB2 and TAB3 to activate TAK1 and IKK. We also show that TAB2 binds to polyubiquitinated RIP following TNFalpha stimulation. These results indicate that polyubiquitin binding domains represent a new class of signaling domains that regulate protein kinase activity through a nonproteolytic mechanism.
journal_name
Mol Celljournal_title
Molecular cellauthors
Kanayama A,Seth RB,Sun L,Ea CK,Hong M,Shaito A,Chiu YH,Deng L,Chen ZJdoi
10.1016/j.molcel.2004.08.008subject
Has Abstractpub_date
2004-08-27 00:00:00pages
535-48issue
4eissn
1097-2765issn
1097-4164pii
S1097-2765(04)00470-8journal_volume
15pub_type
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