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Czub, B, Shah, AZ, Alfano, G, Kruczek, PM, Chakarova, CF and Bhattacharya, SS (2016) TOPORS, a Dual E3 Ubiquitin and Sumo1 Ligase, Interacts with 26 S Protease Regulatory Subunit 4, Encoded by the PSMC1 Gene. PLoS ONE 11:e0148678


The significance of the ubiquitin-proteasome system (UPS) for protein degradation has been highlighted in the context of neurodegenerative diseases, including retinal dystrophies. TOPORS, a dual E3 ubiquitin and SUMO1 ligase, forms a component of the UPS and selected substrates for its enzymatic activities, such as DJ-1/PARK7 and APOBEC2, are important for neuronal as well as retinal homeostasis, respectively. TOPORS is ubiquitously expressed, yet its mutations are only known to result in autosomal dominant retinitis pigmentosa. We performed a yeast two-hybrid (Y2H) screen of a human retinal cDNA library in order to identify interacting protein partners of TOPORS from the retina, and thus begin delineating the putative disease mechanism(s) associated with the retina-specific phenotype resulting from mutations in TOPORS. The screen led to isolation of the 26 S protease regulatory subunit 4 (P26s4/ PSMC1), an ATPase indispensable for correct functioning of UPS-mediated proteostasis. The interaction between endogenous TOPORS and P26s4 proteins was validated by co-immuno-precipitation from mammalian cell extracts and further characterised by immunofluorescent co-localisation studies in cell lines and retinal sections. Findings from hTERT-RPE1 and 661W cells demonstrated that TOPORS and P26s4 co-localise at the centrosome in cultured cells. Immunofluorescent staining of mouse retinae revealed a strong P26s4 reactivity at the interface between retinal pigmented epithelium (RPE) layer and the photoreceptors outer segments (OS). This finding leads us to speculate that P26s4, along with TOPORS, may have a role(s) in RPE phagocytosis, in addition to contributing to the overall photoreceptor and retinal homeostasis via the UPS.


PubMed PMC4752349 Online version:10.1371/journal.pone.0148678




Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status


GO:0005814: centriole



S3 Fig. N-TOPORS localises to the nucleus and centrioles.

Human (h)TERT-RPE1 cells were either co-transfected with V5-tagged N-TOPORS and FLAG-tagged full-length TOPORS (top panel), or with V5-tagged N-TOPORS only (middle and bottom panels). The V5-tagged artificial N-TOPORS fragment co-localised with FLAG-tagged full-length TOPORS (top panel) and endogenous TOPORS (middle panel) at nuclei of hTERT-RPE1 cells and it co-localised with pericentrin at the centrioles.

CACAO 11369


Colocalizes with

GO:0005814: centriole



Figure 2 shows localization of P26s4 at one of the centrioles in dividing cells. The experiments revealed that P26s4 co-localised with both: TOPORS and centriolar markers in dividing (Fig 3), but not in ciliated cells (S2 Fig).

CACAO 11770


See also


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