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  • DBC1 Regulates p53 Stability via Inhibition of CBP-Dependent p53 Polyubiquitination.

DBC1 Regulates p53 Stability via Inhibition of CBP-Dependent p53 Polyubiquitination.

Cell reports (2019-03-21)
Oluwatoyin E Akande, Priyadarshan K Damle, Marius Pop, Nicholas E Sherman, Barbara B Szomju, Larisa V Litovchick, Steven R Grossman
ABSTRACT

The control of p53 protein stability is critical to its tumor suppressor functions. The CREB binding protein (CBP) transcriptional co-activator co-operates with MDM2 to maintain normally low physiological p53 levels in cells via exclusively cytoplasmic E4 polyubiquitination activity. Using mass spectrometry to identify nuclear and cytoplasmic CBP-interacting proteins that regulate compartmentalized CBP E4 activity, we identified deleted in breast cancer 1 (DBC1) as a stoichiometric CBP-interacting protein that negatively regulates CBP-dependent p53 polyubiquitination, stabilizes p53, and augments p53-dependent apoptosis. TCGA analysis demonstrated that solid tumors often retain wild-type p53 alleles in conjunction with DBC1 loss, supporting the hypothesis that DBC1 is selected for disruption during carcinogenesis as a surrogate for p53 functional loss. Because DBC1 maintains p53 stability in the nucleus, where p53 exerts its tumor-suppressive transcriptional function, replacement of DBC1 functionality in DBC1-deleted tumors might enhance p53 function and chemosensitivity for therapeutic benefit.

MATERIALS
Product Number
Brand
Product Description

Millipore
ANTI-FLAG® antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-Myc Tag Antibody, clone 4A6, agarose conjugate, clone 4A6, Upstate®, from mouse