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- Title
Impact of DJ-1 and Helix 8 on the Proteome and Degradome of Neuron-Like Cells.
- Authors
Kern, Ursula; Fröhlich, Klemens; Bedacht, Johanna; Schmidt, Nico; Biniossek, Martin L.; Gensch, Nicole; Baerenfaller, Katja; Schilling, Oliver; Lederkremer, Gerardo Z.
- Abstract
DJ-1 is an abundant and ubiquitous component of cellular proteomes. DJ-1 supposedly exerts a wide variety of molecular functions, ranging from enzymatic activities as a deglycase, protease, and esterase to chaperone functions. However, a consensus perspective on its molecular function in the cellular context has not yet been reached. Structurally, the C-terminal helix 8 of DJ-1 has been proposed to constitute a propeptide whose proteolytic removal transforms a DJ-1 zymogen to an active hydrolase with potential proteolytic activity. To better understand the cell-contextual functionality of DJ-1 and the role of helix 8, we employed post-mitotically differentiated, neuron-like SH-SY5Y neuroblastoma cells with stable over-expression of full length DJ-1 or DJ-1 lacking helix 8 (ΔH8), either with a native catalytically active site (C106) or an inactive site (C106A active site mutation). Global proteome comparison of cells over-expressing DJ-1 ΔH8 with native or mutated active site cysteine indicated a strong impact on mitochondrial biology. N-terminomic profiling however did not highlight direct protease substrate candidates for DJ-1 ΔH8, but linked DJ-1 to elevated levels of activated lysosomal proteases, albeit presumably in an indirect manner. Finally, we show that DJ-1 ΔH8 loses the deglycation activity of full length DJ-1. Our study further establishes DJ-1 as deglycation enzyme. Helix 8 is essential for the deglycation activity but dispensable for the impact on lysosomal and mitochondrial biology; further illustrating the pleiotropic nature of DJ-1.
- Subjects
CELL anatomy; CATHEPSIN B; ZYMOGENS; PROTEOLYTIC enzymes; BIOLOGY; MITOCHONDRIA
- Publication
Cells (2073-4409), 2021, Vol 10, Issue 2, p404
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells10020404