mProX™ Human TNK1 Stable Cell Line

R Balasooriya, Eranga. et al. "Integrating Clinical Cancer and PTM Proteomics Data Identifies a Mechanism of ACK1 Kinase Activation." Molecular cancer research : MCR, 2023.
A machine learning model has been developed to identify new and understudied mut-drivers, potential targets for therapy in cancer treatment, by integrating clinical data and proteomics databases. This model has been applied to 62,746 patient cancers spanning 84 cancer types and has predicted 3,964 oncogenic mutations in 1,148 genes, some of which affect known and unknown post-translational modifications. The model is available as a web application. Non-receptor tyrosine kinases (NRTKs) were studied as a case study, revealing a recurrent mutation in the activated CDC42 kinase-1 (ACK1) that disrupts the Mig6 homology region and ubiquitin-association domains on the ACK1 C-terminus. This mutation is similar to those found in its sister kinase, TNK1, which also disrupts inhibitory motifs and the UBA domain. This study introduces a tool for discovering mut-drivers and identifies a mechanism for hyperactivation in ACK1 and other ACK family kinases. Further implications include the identification of potential oncogenic mutations, including those that affect post-translational modifications, for future research.
R Balasooriya, Eranga. et al. "Integrating Clinical Cancer and PTM Proteomics Data Identifies a Mechanism of ACK1 Kinase Activation." Molecular cancer research : MCR, 2023.
Pubmed: 37847650   DOI: 10.1158/1541-7786.MCR-23-0153

Nawarathnage, Supeshala. et al. "Fusion crystallization reveals the behavior of both the 1TEL crystallization chaperone and the TNK1 UBA domain." Structure (London, England : 1993), 2023.
The study delves into the role of Human thirty-eight-negative kinase-1 (TNK1) in cancer progression, with a focus on its ubiquitin-associated (UBA) domain's influence on TNK1's activity and stability. Remarkably, there is no available molecular structure for this particular UBA domain. Through the fusion of the UBA domain with the 1TEL variant of the translocation ETS leukemia protein sterile alpha motif (TELSAM) crystallization chaperone, researchers were able to produce crystals diffracting up to 1.53 Å. This was achieved using GG and GSGG linkers, enabling the UBA domain to consistently adopt a productive binding configuration with 1TEL and crystallize even at low protein concentrations of 0.2 mg/mL. The findings propose a unique mechanism for 1TEL fusion crystallization, indicating that it requires fewer crystal contacts compared to conventional protein crystals. Furthermore, both modeling and experimental data suggest that the UBA domain might exhibit selectivity for the length and linkages of polyubiquitin chains.
Nawarathnage, Supeshala. et al. "Fusion crystallization reveals the behavior of both the 1TEL crystallization chaperone and the TNK1 UBA domain." Structure (London, England : 1993), 2023.
Pubmed: 37776857   DOI: 10.1016/j.str.2023.09.001