Identification of a novel protein interaction motif in the regulatory subunit of casein kinase 2.

ABSTRACT: Casein kinase 2 (CK2) regulates multiple cellular processes and can promote oncogenesis. Interactions with the CK2? regulatory subunit of the enzyme target its catalytic subunit (CK2? or CK2?') to specific substrates; however, little is known about the mechanisms by which these interactions occur. We previously showed that by binding CK2?, the Epstein-Barr virus (EBV) EBNA1 protein recruits CK2 to promyelocytic leukemia (PML) nuclear bodies, where increased CK2-mediated phosphorylation of PML proteins triggers their degradation. Here we have identified a KSSR motif near the dimerization interface of CK2? as forming part of a protein interaction pocket that mediates interaction with EBNA1. We show that the EBNA1-CK2? interaction is primed by phosphorylation of EBNA1 on S393 (within a polyserine region). This phosphoserine is critical for EBNA1-induced PML degradation but does not affect EBNA1 functions in EBV replication or segregation. Using comparative proteomics of wild-type (WT) and KSSR mutant CK2?, we identified an uncharacterized cellular protein, C18orf25/ARKL1, that also binds CK2? through the KSSR motif and show that this involves a polyserine sequence resembling the CK2? binding sequence in EBNA1. Therefore, we have identified a new mechanism of CK2 interaction used by viral and cellular proteins.

SUBMITTER: Cao JY 

PROVIDER: S-EPMC3911286 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature