Functional analysis of the extraproteasomal ubiquitin receptor Dsk2/UBQLN in Drosophila and human cells

Di Mauro, Gianmarco

Functional analysis of the extraproteasomal ubiquitin receptor Dsk2/UBQLN in Drosophila and human cells

Document Type

Doctoral thesis
Published Version

Author

Di Mauro, Gianmarco

Director

Azorín, F.

Publication Date

2019-02-28

Pages

147 p.

Citation

Di Mauro, G. Functional analysis of the extraproteasomal ubiquitin receptor Dsk2/UBQLN in Drosophila and human cells. Universitat Pompeu Fabra; 2019. handle: http://hdl.handle.net/10803/666204

This citation was generated automatically.

Doctoral program

Programa de doctorat en Biomedicina

Abstract

Dsk2/UBQLN is a conserved extraproteasomal ubiquitin receptor that has been widely described as a protein involved in the ubiquitin proteasome pathway. In Drosophila, this protein has been recently reported in a non-proteolitic function as part of the dHP1c transcription complex together with the zinc finger proteins WOC and ROW, and the heterocromatin protein HP1c. Here we show that the dHP1c complex present a specific functional organization with WOC playing a direct role in the recruitment of dDsk2 to the nuclear compartment. This interaction results in the formation of a WOC-dDsk2 sub-complex that is able to bind chromatin only through ROW. Moreover, we show that UBQLN1, which is the human homologue that shares the highest degree of similarity with dDsk2, is not able to bind chromatin when ectopically expressed in Drosophila and in human-derived cell lines endogenous UBQLN1 is not found associated with chromatin.
Dsk2/UBQLN es un receptor extraproteasomal de ubiquitina altamente conservado que se ha descrito ampliamente como una proteína involucrada en la vía ubiquitina-proteasoma. En Drosophila, se ha descrito recientemente una función no proteolítica para Dsk2 como parte del complejo de transcripción dHP1c conjuntamente con las proteínas “zinc finger” WOC y ROW y la proteína de heterocromatina HP1c. Aquí mostramos que el complejo transcripcional dHP1c tiene una organización funcional, en la que WOC desempeña un papel directo en el reclutamiento de dDsk2 al compartimento nuclear. Esta interacción da como resultado la formación de un sub-complejo estable WOC-dDsk2 que es capaz de unirse a la cromatina solo a través de ROW. Además, mostramos que UBQLN1, que es el homólogo humano que comparte el mayor grado de similitud con dDsk2, no es capaz de unirse a la cromatina cuando se expresa ectópicamente en Drosophila y, en líneas celulares humanas, UBQLN1 no se asocía con la cromatina.