Tbk1-flox Mouse

Tbk1, also known as TANK-binding kinase 1, is a serine/threonine kinase belonging to the non-canonical inhibitor of nuclear factor-κB (IκB) kinase (IKK) family. It plays a crucial role in multiple cellular activities. Primarily, it mediates IRF3/7 activation and NF-κB signaling, regulating inflammatory cytokine production and innate immunity activation. It is also involved in autophagy, mitochondrial metabolism, and cellular proliferation [2].

Genetic approaches have revealed interesting aspects of Tbk1 function. In myeloid cells, Tbk1 alone is dispensable for STING-induced NF-κB responses, as it acts redundantly with IκB kinase ε (IKKε) to drive NF-κB upon STING activation [1]. In cancer, suppression of Tbk1 induces apoptosis specifically in human cancer cell lines that depend on oncogenic KRAS expression, as Tbk1 activates NF-κB anti-apoptotic signals essential for their survival [4]. In TNF signaling, Tbk1 and IKKε phosphorylate the kinase RIPK1 in the TNFR1-SC, preventing TNF-induced cell death [3].

In conclusion, Tbk1 is essential for multiple biological processes, especially in innate immunity and cancer-related cellular survival. Gene-knockout models have been instrumental in revealing its role in these processes, highlighting its potential as a therapeutic target in diseases related to abnormal innate immune responses and cancers, such as those driven by oncogenic KRAS [2,4].