Proteomics

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Identification of protein substrates of a novel proteolysis targeting chimera, PROTAC124 in tongue squamous cell carcinoma cell line CAL-33 overexpressing Leucine Zipper-bearing Kinase (LZK).

ABSTRACT: Head and neck squamous cell carcinomas (HNSCC) are aggressive epithelial tumors with a low and unchanged 50% 5-year survival rate. MAP3K13 gene encoding Leucine Zipper-bearing Kinase (LZK) is often amplified in HNSCC patients and can be an oncogenic driver for tumorigenesis. In order to reduce catalytic and non-catalytic functions of LZK we synthetized novel, potent and selective degrader of LZK protein using proteolysis targeting chimera technology. We confirmed efficiency and specificity of our PROTAC by shotgun proteomic analysis.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Head And Neck Squamous Cell Carcinoma Cell Line

SUBMITTER: Remigiusz Serwa  

LAB HEAD: Anna Marusiak

PROVIDER: PXD057778 | Pride | 2025-06-16

REPOSITORIES: Pride

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Publications

Discovery of potent and selective PROTACs for the protein kinase LZK for the treatment of head and neck cancer.

Katerji Meghri M   Bergman Knickole L KL   Lindberg Eric E   Rubin Maxine R MR   Afifi Marwa M   Funk Amy L AL   Woodroofe Carolyn C CC   Nyswaner Katherine K   Karpińska Kamila K   Serwa Remigiusz R   Cappell Steven D SD   Marusiak Anna A   Swenson Rolf E RE   Brognard John F JF  

The Journal of biological chemistry 20250327 5

Leucine zipper-bearing kinase (LZK) is overexpressed in 20% of head and neck squamous cell carcinoma (HNSCC) cases and has emerged as a promising therapeutic target in this cancer subtype. LZK promotes HNSCC survival and proliferation by stabilizing c-MYC and GOF-p53 in kinase-dependent and -independent manners, respectively. Herein, we developed a new series of LZK degraders utilizing proteolysis-targeting chimera (PROTAC) technology by modulating the linker region or LZK warhead of LZK-targeti  ...[more]

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