Metabolic Regulation of Caspase 2 in Breast Cancer
Abstract
Our research focuses on the apical apoptotic enzyme caspase 2 (C2), which has been proposed as a critical activating protease for breast cancer chemotherapeutic agents such as doxorubicin and etoposide. Our lab has previously shown that C2 is held inactive by nutrient flux through the pentose phosphate pathway via phosphorylation at serine 135, which is mediated by calmodulin-dependent protein kinase II (CaMKII). We now report recent exciting advancements in the understanding of caspase-2 metabolic regulation using Xenopus laevis egg extract: as nutrient levels wane and NADPH/CaMKII activity drops, the acidic phosphoserine-binding protein 14-3-3zeta is released from caspase-2, leaving caspase-2 vulnerable to PP1-mediated dephosphorylation and subsequent activation. Importantly, this mechanism appears to be conserved in mammalian oocytes, further supporting that, in fact, caspase-2 is likely to be metabolically regulated even in mammals. This work has been accepted for publication in the June 16, 2009, edition of Developmental Cell. In extending these findings to breast cancer, we have produced phospho-specific antibodies to potential mouse caspase-2 phosphorylation sites, and are currently examining the metabolic regulation of these phosphoryation sites in somatic cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2009
- Accession Number
- ADA504651
Entities
People
- Marisa Buchakjian
Organizations
- Duke University