Lysine 68 acetylation directs MnSOD as a tetrameric detoxification complex versus a monomeric tumor promoter.

ABSTRACT: Manganese superoxide dismutase (MnSOD) functions as a tumor suppressor; however, once tumorigenesis occurs, clinical data suggest MnSOD levels correlate with more aggressive human tumors, implying a potential dual function of MnSOD in the regulation of metabolism. Here we show, using in vitro transformation and xenograft growth assays that the MnSOD-K68 acetylation (Ac) mimic mutant (MnSOD^K68Q) functions as a tumor promoter. Interestingly, in various breast cancer and primary cell types the expression of MnSOD^K68Q is accompanied with a change of MnSOD's stoichiometry from a known homotetramer complex to a monomeric form. Biochemical experiments using the MnSOD-K68Q Ac-mimic, or physically K68-Ac (MnSOD-K68-Ac), suggest that these monomers function as a peroxidase, dis

SUBMITTER: Zhu Y 

PROVIDER: S-EPMC6546705 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature