LIMD1 is induced by and required for LMP1 signaling, and protects EBV-transformed cells from DNA damage-induced cell death

Oncotarget
Ling WangS Ning

Abstract

LIMD1 (LIM domain-containing protein 1) is considered as a tumor suppressor, being deregulated in many cancers to include hematological malignancies; however, very little is known about the underlying mechanisms of its deregulation and its roles in carcinogenesis. Epstein-Barr Virus (EBV) is associated with a panel of malignancies of lymphocytic and epithelial origin. Using high throughput expression profiling, we have previously identified LIMD1 as a common marker associated with the oncogenic transcription factor IRF4 in EBV-related lymphomas and other hematological malignancies. In this study, we have identified potential conserved IRF4- and NFκB-binding motifs in the LIMD1 gene promoter, and both are demonstrated functional by promoter-reporter assays. We further show that LIMD1 is partially upregulated by EBV latent membrane protein 1 (LMP1) via IRF4 and NFκB in EBV latency. As to its role in the setting of EBV latent infection, we show that LIMD1 interacts with TRAF6, a crucial mediator of LMP1 signal transduction. Importantly, LIMD1 depletion impairs LMP1 signaling and functions, potentiates ionomycin-induced DNA damage and apoptosis, and inhibits p62-mediated selective autophagy. Taken together, these results show that ...Continue Reading

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Citations

Oct 20, 2018·Current Cancer Drug Targets·Shunbin Ning, Ling Wang
Jun 14, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Javid Sadri NahandHamed Mirzaei
Oct 26, 2021·Journal of Molecular Biology·Andrew LopezOliver I Fregoso

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Methods Mentioned

BETA
immunoprecipitation
ChIP
PCR
ubiquitination
flow cytometry
transfection
transfections
Assay

Software Mentioned

Graphpad Prism

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