Human CHUK blocking peptide

Lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are two distinct and predominant types of human lung cancer. I kappa B kinase alpha (IKK alpha) has been shown to suppress lung SCC development, but its role in ADC is unknown. We found inactivating mutations and homologous or hemizygous deletions in the CHUK locus, which encodes IKK alpha, in human lung ADCs. The CHUK deletions significantly reduced the survival time of patients with lung ADCs harboring KRAS mutations. In mice, lung-specific Ikk alpha ablation (Ikk alpha(Delta Lu)) induces spontaneous ADCs and promotes Kras(G12D)-initiated ADC development, accompanied by increased cell proliferation, decreased cell senescence, and reactive oxygen species (ROS) accumulation. IKK alpha deletion up-regulates NOX2 and down-regulates NRF2, leading to ROS accumulation and blockade of cell senescence induction, which together accelerate ADC development. Pharmacologic inhibition of NADPH oxidase or ROS impairs Kras(G12D)-mediated ADC development in Ikk alpha(Delta Lu) mice. Therefore, IKK alpha modulates lung ADC development by controlling redox regulatory pathways. This study demonstrates that IKK alpha functions as a suppressor of lung ADC in human and mice through a unique mechanism that regulates tumor cell-associated ROS metabolism.

Clostridium perfringens type C (C. perfringens type C) is one of the main microbial pathogens responsible for piglet diarrhea worldwide, causing substantial economic losses for pig-rearing industries. The mitogen-activated protein kinase (MAPK) signaling pathway is a key regulator of inflammatory bowel disease, especially necrotic enteritis. However, whether and how the MAPK signaling pathway is involved in regulating the process of piglet diarrhea when challenged by C. perfringens type C are still unknown. Here, we screened 38 differentially expressed genes (DEGs) in piglets' ileum tissues experimentally infected with C. perfringens type C that were enriched in the Sus scrofa MAPK signaling pathway, based on our previous transcriptome data. Of these DEGs, 12 genes (TRAF2, MAPK8, and GADD45G, among others) were upregulated whereas 26 genes (MAPK1, TP53, and CHUK, among others) were downregulated in the infected group. Our results showed that MAPK1, TP53, MAPK8, MYC, and CHUK were in the core nodes of the PPI network. Additionally, we obtained 35 lncRNAs from the sequencing data, which could be trans-targeted to MAPK signaling pathway genes and were differentially expressed in the ileum tissues infected with C. perfringens. We used qRT-PCR to verify the expression levels of genes and lncRNAs related to the MAPK signaling pathway; their expression patterns were consistent with RNA sequencing data. Our results provide strong support for deeply exploring the role of the MAPK signaling pathway in diarrhea caused by C. perfringens type C.