Numerous studies, published over many years, have established the key role that the IκB kinase (IKK) subunits, α and β, play in regulating the Nuclear Factor κB (NF-κB) pathway. This research generally concluded that their functions can be separated, with IKKβ being the critical regulator of the canonical NF-κB pathway, while IKKα functions as the key activating kinase for the non-canonical pathway. However, other roles for these kinases have been described and several reports concluded that this separation of their functions may not always be the case. This commentary discusses the recent report by Biochem J. 479, 305–325, who elegantly demonstrate that in KRAS driven colorectal cancer cell lines, IKKα is an important regulator of the canonical NF-κB pathway. As is so often the case with trying to understand the complexity of NF-κB signalling, cellular context is everything.
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The cover image shows the crystal structure of AMPK a2b1g1 complexed with the pan activator MSG011. The inset surface representation details architecture of the MSG011 binding site, formed between the AMPK alpha-kinase domain (green) and beta-carbohydrate binding module (CBM, cyan). Explore more with Ovens and colleagues, “Structure-function analysis of the AMPK activator SC4 and identification of a potent pan AMPK activator” on pages 1181-1204.
Commentary| June 01 2022
Alphabetti kinase Spaghetti: the complex roles of IKKα and β in the canonical NF-κB pathway
In Collection Cell death and survival
Neil D. Perkins
Newcastle University Biosciences Institute, Wolfson Childhood Cancer Research Centre, Newcastle University, Level 6, Herschel Building, Brewery Lane, Newcastle upon Tyne NE1 7RU, U.K.
Correspondence: Neil D. Perkins (firstname.lastname@example.org)
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Biochem J (2022) 479 (11): 1121–1126.
March 23 2022
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This is a commentary on: IKKα plays a major role in canonical NF-κB signalling in colorectal cells
Neil D. Perkins; Alphabetti kinase Spaghetti: the complex roles of IKKα and β in the canonical NF-κB pathway. Biochem J 17 June 2022; 479 (11): 1121–1126. doi: https://doi.org/10.1042/BCJ20220023
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