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SERBP1 deacetylation inhibits ferroptosis to promote KSHV-induced cellular transformation by decaying lipoyltransferase 2 mRNA

ABSTRACT: Ferroptosis, a defensive strategy employed by the host to restrict pathogenic infections, has been implicated in the development and therapeutic responses of various types of tumors. However, the role of ferroptosis in KSHV-induced malignant tumors remains elusive. A steadily growing number of non-histone proteins have been identified as acetylation targets, their functions have yet to be revealed. In this study, we obtained a marked disparity in the landscape of acetylation between MM and KSHV-transformed MM (KMM) cells. SERBP1 deacetylation was upregulated in KMM cells and contributed to KSHV-induced cellular transformation by inhibiting ferroptosis. Mechanistically, KSHV-encoded viral interleukin-6 (vIL-6) hijacks SIRT3, a mitochondrial NAD+-dependent deacetylase, to interact with SERBP1 leading to the deacetylation of SERBP1. Deacetylated SERBP1 exhibits reduced binding to Lipt2 mRNA, which promotes Lipt2 mRNA degradation, resulting in ferroptosis inhibition. Our findings unveil a novel role of SERBP1 deacetylation in regulating ferroptosis and KSHV-induced cellular transformation and identify potential new therapeutic targets for KSHV infection and KSHV-induced cancers.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE241111 | GEO | 2023/08/22

REPOSITORIES: GEO

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