Inhibition of human mitochondrial peptide deformylase causes apoptosis in c-myc-overexpressing hematopoietic cancers.

ABSTRACT: Inhibition of human mitochondrial peptide deformylase (HsPDF) depolarizes the mitochondrial membrane, reduces mitochondrial protein translation and causes apoptosis in Burkitt's lymphoma. We showed that HsPDF mRNA and protein levels were overexpressed in cancer cells and primary acute myeloid leukemia samples. Myc regulates mitochondria and metabolism; we also demonstrated c-myc regulated the expression of HsPDF, likely indirectly. Inhibition of HsPDF by actinonin blocked mitochondrial protein translation and caused apoptotic death of myc-positive Burkitt's lymphoma, but not myc-negative B cells. Inhibition of mitochondrial translation by chloramphenicol or tetracycline, structurally different inhibitors of the mitochondrial ribosome, which is upstream of deformylase activity, followed by

SUBMITTER: Sheth A 

PROVIDER: S-EPMC3973238 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature