Transcriptomics

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Stabilization of c-Myc protein by CAMKIIγ promotes T-cell lymphoma


ABSTRACT: Although high c-Myc protein expression is observed alongside c-Myc gene amplification in some cancers, in most cases protein overexpression occurs while the amplified gene is largely absent, e.g. T-cell lymphoma (TCL). Here, Ca2+/calmodulin-dependent protein kinase II γ (CAMKIIγ) was shown to stabilize c-Myc protein by directly phosphorylating at serine 62 (S62), which represents a hitherto unknown mechanism of c-Myc protein overexpression. Further, CAMKIIγ was shown to be essential for tumor maintenance. Inhibiting CAMKIIγ with a potent CAMKIIγ-specific inhibitor destabilized c-Myc and reduced tumor burden dramatically. Importantly, high CAMKIIγ in clinical patient specimens positively correlated with increased c-Myc / pS62-c-Myc expression. Together, the CAMKIIγ:c-Myc axis critically influences the development and maintenance of TCL, and represent a novel therapeutic target for TCL.

ORGANISM(S): Mus musculus

PROVIDER: GSE99364 | GEO | 2017/05/27

SECONDARY ACCESSION(S): PRJNA388202

REPOSITORIES: GEO

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