Identification and characterization of a novel spliced form of the meq transcript in lymphoblastoid cell lines derived from Marek's disease tumours

Abstract

In tumour cell lines established from Marek's disease (MD) lymphomas L-meqis consistently expressed. It contains a 180 bp insertion encoding additional copies of the proline-rich repeat in themeqopen reading frame and its product may contribute to the maintenance of MD virus (MDV) latency. In this study, we identified a novel spliced form of themeqtranscript in MD-derived lymphoblastoid cell lines and in MDV-infected cells. This transcript, termed Δmeq, encodes an N-terminal 98 aa of the Meq protein and lacks part of the basic leucine zipper (bZIP) and transactivation domains. In MD cell lines, transcription of L-meqwas significantly downregulated, while that of the Δmeqtranscript was upregulated during apoptosis. These observations were also confirmed at the protein expression level. Reporter assays usingmeq- andinterleukin-2(IL-2)-promoter-driven luciferase vectors revealed that ΔMeq suppressed transactivation by L-Meq or Meq in a dose-dependent manner. Immunoprecipitation confirmed that ΔMeq was associated with L-Meq or Meq physically. These results suggest that ΔMeq could be involved in apoptosis in MD cell lines as it works as a negative regulator of L-Meq and Meq by direct interaction.