Stabilization of the c-Myc Protein by CAMKIIγ Promotes T Cell Lymphoma.

Abstract:

:Although high c-Myc protein expression is observed alongside MYC amplification in some cancers, in most cases protein overexpression occurs in the absence of gene amplification, e.g., T cell lymphoma (TCL). Here, Ca2+/calmodulin-dependent protein kinase II γ (CAMKIIγ) was shown to stabilize the c-Myc protein by directly phosphorylating it at serine 62 (S62). Furthermore, CAMKIIγ was shown to be essential for tumor maintenance. Inhibition of CAMKIIγ with a specific inhibitor destabilized c-Myc and reduced tumor burden. Importantly, high CAMKIIγ levels in patient TCL specimens correlate with increased c-Myc and pS62-c-Myc levels. Together, the CAMKIIγ:c-Myc axis critically influences the development and maintenance of TCL and represents a potential therapeutic target for TCL.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Gu Y,Zhang J,Ma X,Kim BW,Wang H,Li J,Pan Y,Xu Y,Ding L,Yang L,Guo C,Wu X,Wu J,Wu K,Gan X,Li G,Li L,Forman SJ,Chan WC,Xu R,Huang W

doi

10.1016/j.ccell.2017.06.001

subject

Has Abstract

pub_date

2017-07-10 00:00:00

pages

115-128.e7

issue

1

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(17)30251-9

journal_volume

32

pub_type

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