LZTR1 is a Melanoma Oncogene that Promotes Cell Growth and Inhibits Apoptosis Under Stress

ABSTRACT: LZTR1 is known to act as a tumor suppressor in glioma, acting as an adaptor protein for Cullin 3 (CUL3) ubiquitin ligase. However, we demonstrated that LZTR1 is amplified in acral melanomas, and is required for melanoma cell proliferation and anchorage-independent growth. To understand the molecular mechanisms by which LZTR1 amplification promotes melanomas, we carried out proximity biotinylation by TurboID and co-immunoprecipitation assays. We identified LZTR1 proximal proteins associated not only with ubiquitination and autophagy, but also with de-ubiquitination, focal adhesion, stress response, and actin cytoskeleton. LZTR1 is not “just” an adaptor protein for Cullin 3 (CUL3) ubiquitin ligase complex but is a hub for additional molecular functions such as de-ubiquitination and actin organization that confer context-dependent tumor promoting activity. Downregulation of LZTR1 is therefore a novel cell death mechanism that can be targeted for melanoma therapy.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

DISEASE(S): Acral Lentiginous Melanoma

SUBMITTER: Haomiao Su  

LAB HEAD: Sarah A Slavoff

PROVIDER: PXD054157 | Pride | 2025-10-13

REPOSITORIES: Pride