The Gpn3 Q279* cancer‐associated mutant inhibits Gpn1 nuclear export and is deficient in RNA polymerase II nuclear targeting. Issue 21 (11th October 2017)

• Record Type: Journal Article
• Authors: Barbosa‐Camacho, Angel A.; Méndez‐Hernández, Lucía E.; Lara‐Chacón, Bárbara; Peña‐Gómez, Sonia G.; Romero, Violeta; González‐González, Rogelio; Guerra‐Moreno, José A.; Robledo‐Rivera, Angélica Y.; Sánchez‐Olea, Roberto; Calera, Mónica R.
• Is Part Of: FEBS letters. Volume 591:Issue 21(2017)
• Page Start: 3555
• Page End: 3566
• Publication Date: 2017-10-11
• Subjects: colon and skin cancer -- Gpn1 nuclear export -- Gpn3 -- PDZ‐binding motif; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.12856
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Gpn3 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 RNAi, we replaced endogenous Gpn3 by wt or Q279* RNAi‐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. Abstract :