Distinct Ubiquitination Cascades Act on the Peroxisomal Targeting Signal Type 2 Co‐receptor Pex18p. (7th October 2013)

• Record Type: Journal Article
• Authors: El Magraoui, Fouzi; Brinkmeier, Rebecca; Schrötter, Andreas; Girzalsky, Wolfgang; Müller, Thorsten; Marcus, Katrin; Meyer, Helmut E.; Erdmann, Ralf; Platta, Harald W.
• Is Part Of: Traffic. Volume 14:Number 12(2013:Dec.)
• Page Start: 1290
• Page End: 1301
• Publication Date: 2013-10-07
• Subjects: peroxisomal biogenesis -- Pex18p -- Pex4p -- PTS‐receptor -- RING E3 enzyme -- ubiquitination; Biological transport -- Periodicals; 571.6
• DOI: 10.1111/tra.12120
• Languages: English
• ISSNs: 1398-9219

Abstract

Abstract : Peroxisomal matrix protein import is facilitated by cycling receptors that recognize their cargo proteins in the cytosol by a peroxisomal targeting sequence (PTS) and ferry them to the peroxisomal membrane. Subsequently, the cargo is translocated into the peroxisomal lumen, whereas the receptor is released to the cytosol for further rounds of protein import. This cycle is controlled by the ubiquitination status of the receptor, which is best understood for the PTS1‐receptor. While polyubiquitination of PTS‐receptors results in their proteasomal degradation, the monoubiquitinated PTS‐receptors are exported to the cytosol and recycled for further rounds of protein import. Here, we describe the identification of two ubiquitination cascades acting on the PTS2 co‐receptor Pex18p. Using in vivo and in vitro approaches, we demonstrate that the polyubiquitination of Pex18p requires the ubiquitin‐conjugating enzyme (E2) Ubc4p, which cooperates with the RING (really interesting new gene)‐type ubiquitin‐protein ligases (E3) Pex2p as well as Pex10p. Monoubiquitination of Pex18p depends on the E2 enzyme Pex4p (Ubc10p), which functions in concert with the E3 enzymes Pex12p and Pex10p. Our findings for the PTS2‐pathway complement the data on PTS1‐receptor ubiquitination and add up to a unified concept of the ubiquitin‐based regulation of peroxisomal import . Abstract : The peroxisomal targeting signal type 2 co‐receptor Pex18p is polyubiquitinated on lysine residues and monoubiquitinated on a conserved cysteine. In this study, we have identified the two corresponding ubiquitination cascades that catalyze these modifications. We demonstrate that polyubiquitination of Pex18p requires the ubiquitin‐conjugating enzyme (E2) Ubc4p, which cooperates with the RING (really interesting new gene)‐type ubiquitin‐protein ligases (E3) Pex2p as well as Pex10p. Monoubiquitination of Pex18p is catalyzed by the E2 enzyme Pex4p which acts in concert with the E3 enzymes Pex12p and Pex10p.