Abstract
Transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) is a member of the mitogen-activated protein kinase kinase kinase (MAPKKK) family that is activated by growth factors and cytokines such as TGF-β, IL-1β, and TNF-α, and mediates a wide range of biological processes through activation of the nuclear factor-κB (NF-κB) and the mitogen-activated protein (MAP) kinase signaling pathways. It is well established that activation status of TAK1 is tightly regulated by forming a complex with its binding partners, TAK1-binding proteins (TAB1, TAB2, and TAB3). Interestingly, recent evidence indicates the importance of post-translational modifications (PTMs) of TAK1 and TABs in the regulation of TAK1 activation. To date, a number of PTMs of TAK1 and TABs have been revealed, and these PTMs appear to fine-tune and coordinate TAK1 activities depending on the cellular context. This review therefore focuses on recent advances in the understanding of the PTMs of the TAK1-TAB complex.
Highlights
Transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1, known as MAP3K7), a member of the mitogen-activated protein (MAP) kinase kinase kinase (MAP3K) family, was originally identified as a protein kinase that is activated by TGF-β and bone morphogenic protein (BMP) [1]
Subsequent studies have revealed that TAK1 is activated by a wide variety of proinflammatory mediators, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, toll-like receptor (TLR) ligands, and T-cell receptor (TCR) and B-cell receptor (BCR) antigens [2,3]
Ectopic expression of RBCK1 promoted ubiquitination and proteasome-dependent degradation of TAB2 and TAB3, and knockdown of RBCK1 increased nuclear factor-κB (NF-κB) activation induced by IL-1β and TNF-α, suggesting that RBCK1 negatively regulates TAK1 signaling via K48-linked polyubiquitination and degradation of TAB2 and TAB3 [91]
Summary
Transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1, known as MAP3K7), a member of the mitogen-activated protein (MAP) kinase kinase kinase (MAP3K) family, was originally identified as a protein kinase that is activated by TGF-β and bone morphogenic protein (BMP) [1]. The activation of these two transcriptional factors is predominantly regulated by TAK1-dependent signaling cascade [2,3] (Figure 1). It has been reported that TAK1 is activated by various stresses including DNA damage and osmotic shock, indicating the involvement of TAK1 in stress-response signaling [2,5,6]. 22 amino acids exhibits constitutive activity [1], and a peptide containing N-terminal 77 amino acids of TAK1 can inhibit TAK1 activation [15]. The upstream regulators of TAK1 depend on the type of stimulus, the interaction with TABs is an essential step for TAK1 activation. We focus on the PTMs of the TAK1-TAB complex, which may play critical roles in the regulation of TAK1-dependent signaling
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