In this work we have critically evaluated the role of lysosomes and lysosomal cathepsins in three major types of cell death, apoptosis, necrosis and autophagy, although the latter is probably not a cell death mechanism, but a survival one. The article is based also on our previous results.
COBISS.SI-ID: 22640935
Recently opposing effects of cysteine protease inhibitors, the human cystatins, on neurodegeneration have been reported. Human cystatin C is a risk factor for late-onset Alzheimer's disease (AD), whereas human stefin B (cystatin B) has no direct involvement in AD. Some reports claim that cystatin C binds soluble Abeta, making transgenic animals healthier, others, in contrast, that deleting cystatins genes may contribute to amyloid pathology in animal models of AD. In this work a critical overview on the role of cystatins in these processes is given.
COBISS.SI-ID: 22609959
Proteins from the cystatin superfamily are the major endogenous inhibitors of cysteine cathepsins and legumain that have critical role in numerous physiological processes, including protein degradation and antigen presentation. We traced the genesis and expansion of the cystatin superfamily through comparative genomic and phylogenomic analyses. This study challenges the current view on the classification, origin and evolution of the cystatin superfamily and provides valuable insights into their functional diversification.
COBISS.SI-ID: 23152679
Extremely important was the discovery of the protein fascin as a critical regulator of activity of the protein Rab35, which is one of the key regulators of actin bundling. In this study, affinity chromatography was used to isolate Rab35-interacting proteins, which were then identified using mass spectrometry. Among them fascin was identified and later validated as the critical effector of Rab35. Introduction of this method is of major importance for future work.
COBISS.SI-ID: 22849063
Using different methods we demonstrated in this article that procathepsin B possess a small, but significant catalytic activity, which is sufficient to trigger autocatalytic activation of procathepsin B. We suggest that such a model applies to all cysteine cathepsins and is of physiological relevance in various disease states including cancer, RA and OA.
COBISS.SI-ID: 22392615