Background: Protein quality control proteases degrade damaged proteins and protein fragments. Results:The human serine protease HTRA1 degrades tau aggregates and is induced by its substrates. Conclusion: A member of the widely conserved HtrA family is involved in protein quality control in mammalian cells. Significance: HTRA1 might function as a tau protease in vivo.

BackgroundIncreased numbers and improperly positioned centrosomes, aneuploidy or polyploidy, and chromosomal instability are frequently observed characteristics of cancer cells. While some aspects of these events and the checkpoint mechanisms are well studied, not all players have yet been identified. As the role of proteases other than the proteasome in tumorigenesis is an insufficiently addressed question, we investigated the epigenetic control of the widely conserved protease HTRA1 and the phenotypes of deregulation.MethodsMouse embryonal fibroblasts and HCT116 and SW480 cells were used to study the mechanism of epigenetic silencing of HTRA1. In addition, using cell biological and genetic methods, the phenotypes of downregulation of HTRA1 expression were investigated.ResultsHTRA1 is epigenetically silenced in HCT116 colon carcinoma cells via the epigenetic adaptor protein MBD2. On the cellular level, HTRA1 depletion causes multiple phenotypes including acceleration of cell growth, centrosome amplification and polyploidy in SW480 colon adenocarcinoma cells as well as in primary mouse embryonic fibroblasts (MEFs).ConclusionsDownregulation of HTRA1 causes a number of phenotypes that are hallmarks of cancer cells suggesting that the methylation state of the HtrA1 promoter may be used as a biomarker for tumour cells or cells at risk of transformation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2425-8) contains supplementary material, which is available to authorized users.

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