The Gpn3 Q279* cancer‐associated mutant inhibits Gpn1 nuclear export and is deficient in RNA polymerase II nuclear targeting
2017; Wiley; Volume: 591; Issue: 21 Linguagem: Inglês
10.1002/1873-3468.12856
ISSN1873-3468
AutoresAngel A. Barbosa‐Camacho, Lucía E. Méndez‐Hernández, Bárbara Lara‐Chacón, Sonia G. Peña‐Gómez, Violeta Romero, Rogelio González‐González, José A. Guerra‐Moreno, Angélica Y. Robledo‐Rivera, Roberto Sánchez‐Olea, Mónica R. Calera,
Tópico(s)Nuclear Structure and Function
ResumoGpn3 is required for RNA polymerase II ( RNAPII ) nuclear targeting. Here, we investigated the effect of a cancer‐associated Q279* nonsense mutation in Gpn3 cellular function. Employing RNA i, we replaced endogenous Gpn3 by wt or Q279* RNA i‐resistant Gpn3R in epithelial model cells. RNAPII nuclear accumulation and transcriptional activity were markedly decreased in cells expressing only Gpn3R Q279*. Wild‐type Gpn3R localized to the cytoplasm but a fraction of Gpn3R Q279* entered the cell nucleus and inhibited Gpn1‐ EYFP nuclear export. This property and the transcriptional deficit in Gpn3R Q279*‐expressing cells required a PDZ ‐binding motif generated by the Q279* mutation. We conclude that an acquired PDZ ‐binding motif in Gpn3 Q279* caused Gpn3 nuclear entry, and inhibited Gpn1 nuclear export and Gpn3‐mediated RNAPII nuclear targeting.
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