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. Author manuscript; available in PMC: 2019 Sep 18.
Published in final edited form as: FEBS J. 2018 May 14;285(18):3324–3336. doi: 10.1111/febs.14492

Figure 2. Tax hijacks RNF8 and LUBAC to activate TAK1 and IKK, and multiple downstream signaling pathways.

Figure 2

Tax interacts with and stimulates RNF8 and LUBAC to assemble hybrid K63-linked and M1-linked (linear) polyubiquitin chains as signaling scaffolds for TAK1 and IKK recruitment and activation. TAK1, in turn, activates mitogen-activated protein kinase kinases (MKKs) and IKK, and downstream p38 kinase, c-Jun kinase (JNK), canonical NF-κB. and mammalian target of rapamycin (mTOR) pathways. Whether the mislocalization and aberrant activation of RNF8 and LUBAC lead to covalent modifications of cellular proteins by K63-linked and M1-linked (linear) polyubiquitin chains remains unclear. Whether the over-abundance of K63-linked, M1-linked, and hybrid polyubiquitin chains cause sequestration/disruption of critical cellular processes such as DNA damage repair and cytokinesis also remain to be determined.