Chuk, also known as Conserved Helix-Loop-Helix Ubiquitous Kinase and IκB kinase α, is a gene encoding a protein with a serine-threonine kinase catalytic domain. It is highly conserved in evolution and ubiquitously expressed. Chuk is involved in the NF-κB signaling pathway, which is crucial for coordinating immune responses, inflammation, and cell survival [2].

In two independent in vivo lung cancer models, Chuk/IKK-α acts as a major non-small-cell lung cancer (NSCLC) tumor suppressor. Ablation of IKKα in alveolar type II lung epithelial cells of a transgenic mouse strain led to an increase in the number and size of lung adenomas in response to the chemical carcinogen urethane. In human NSCLC lines, IKKα knockdown enhanced their growth as tumor xenografts in immune-compromised mice. Bioinformatics and validation experiments showed that IKKα loss up-regulated activated HIF-1-α protein, enhancing NSCLC tumor growth under hypoxic conditions [1].

In conclusion, Chuk plays an essential role in the NF-κB signaling pathway, with implications for immune response and inflammation. Its role as a tumor suppressor in NSCLC, as revealed by gene-knockout mouse models, provides valuable insights into the disease mechanism. Understanding Chuk's function may offer potential strategies for treating NSCLC and other diseases related to NF-κB pathway dysregulation.

References:

1. Chavdoula, Evangelia, Habiel, David M, Roupakia, Eugenia, Kolettas, Evangelos, Marcu, Kenneth B. 2019. CHUK/IKK-α loss in lung epithelial cells enhances NSCLC growth associated with HIF up-regulation. In Life science alliance, 2, . doi:10.26508/lsa.201900460. https://pubmed.ncbi.nlm.nih.gov/31792060/

2. Connelly, M A, Marcu, K B. . CHUK, a new member of the helix-loop-helix and leucine zipper families of interacting proteins, contains a serine-threonine kinase catalytic domain. In Cellular & molecular biology research, 41, 537-49. doi:. https://pubmed.ncbi.nlm.nih.gov/8777433/