Journal article

Cystatin D Locates in the Nucleus at Sites of Active Transcription and Modulates Gene and Protein Expression

Gemma Ferrer-Mayorga, Silvia Alvarez-Diaz, Noelia Valle, Javier De Las Rivas, Marta Mendes, Rodrigo Barderas, Francesc Canals, Olga Tapia, J Ignacio Casal, Miguel Lafarga, Alberto Munoz

JOURNAL OF BIOLOGICAL CHEMISTRY | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2015

Abstract

Cystatin D is an inhibitor of lysosomal and secreted cysteine proteases. Strikingly, cystatin D has been found to inhibit proliferation, migration, and invasion of colon carcinoma cells indicating tumor suppressor activity that is unrelated to protease inhibition. Here, we demonstrate that a proportion of cystatin D locates within the cell nucleus at specific transcriptionally active chromatin sites. Consistently, transcriptomic analysis show that cystatin D alters gene expression, including that of genes encoding transcription factors such as RUNX1, RUNX2, and MEF2C in HCT116 cells. In concordance with transcriptomic data, quantitative proteomic analysis identified 292 proteins differential..

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Grants

Awarded by Spanish Ministry of Economy and Competitiveness-Fondo Europeo de Desarrollo Regional (FEDER)


Awarded by Comunidad de Madrid Grant Colomics2


Awarded by FEDER-Instituto de Salud Carlos III Grant


Funding Acknowledgements

This work was supported by Spanish Ministry of Economy and Competitiveness-Fondo Europeo de Desarrollo Regional (FEDER) Grant SAF2013-43468-R, Comunidad de Madrid Grant Colomics2 S2010/BMD-2344, and FEDER-Instituto de Salud Carlos III Grant RD12/0036/0021. The authors declare that they have no conflicts of interest with the contents of this article.