Lysosomal integral membrane protein type-2 (LIMP-2/SCARB2) is a substrate of cathepsin-F, a cysteine protease mutated in type-B-Kufs-disease

Peters, Judith C.; Rittger, Andrea; Knabbe, Johannes; Zunke, Friederike; Rothaug, Michelle; Damme, Markus; Berkovic, Samuel F.; Blanz, Judith; Säftig, Paul; Schwake, Michael

doi:10.1016/j.bbrc.2014.12.111

Cited by 14 publications

(8 citation statements)

References 39 publications

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“…LIMPII regulates endosomal biogenesis and alters prostate cells, and investigating these biomarkers may be a novel method to aid in the diagnosis and prognosis of prostate cancer [39]. Recently, it has been shown that many lysosomal membrane proteins undergo proteolysis, which is mainly mediated by cathepsin proteases like cathepsin-F, indicating lysosomal LIMPII as substrate of cathepsin-F [40]. However, in this study, an increased expression of CD36 and decreased expression of LIMPII was observed.…”

Section: Discussioncontrasting

confidence: 58%

Physical resistance training-induced changes in lipids metabolism pathways and apoptosis in prostate

et al. 2020

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Background: Altered lipid metabolism is an important characteristic of neoplastic cells, with androgens and growth factors being major regulatory agents of the lipid metabolism process. We investigated the effect of physical resistance training on lipid metabolism and apoptosis in the adult Wistar rat prostate. Methods: Two experimental groups represented sedentary and physical resistance training. Three days per week for 13 weeks, rats performed jumps in water carrying a weight load strapped to their chests as part of a physical resistance exercise protocol. Two days after the last training session, rats were anesthetized and sacrificed for blood and prostate analysis. Results: Physical exercise improved feeding efficiency, decreased weight gain, regulated the serum-lipid profile, and modulated insulin-like growth factor-1 (IGF-1) and free testosterone concentration. Furthermore, upregulation of cluster of differentiation 36 (CD36), sterol regulatory element binding protein-1 (SREBP-1), sterol regulatory elementbinding protein cleavage-activating protein (SCAP), and reduced lysosome membrane protein (LIMPII) expression were also observed in the blood and prostates of trained rats. Consistent with these results, caspase-3 expression was upregulating and the BCL-2/Bax index ratio was decreased in trained rats relative to sedentary animals. Conclusions: In this work, physical resistance training can alter lipid metabolism and increase markers of apoptosis in the prostate, suggesting physical resistance training as a potential novel therapeutic strategy for treating prostate cancer.

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Section: Discussioncontrasting

confidence: 58%

Physical resistance training-induced changes in lipids metabolism pathways and apoptosis in prostate

et al. 2020

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“…To date, nine mutations with recessive inheritance are known to cause CLN13: six missense mutations (p.Gln321Arg, p.Gly458Ala, p.Ser480Leu, p.Tyr231Cys, p.Ile404Thr, and p.Cys326Phe), a nonsense mutation c.416C > A (p.S139*), a frameshift mutation (p.Ser319Leufs*27), and a mutation preventing the correct splicing of CTSF mRNA (c.213 + 1G>C) [134][135][136][137]. It has been shown that disease-causing CTSF mutants fail to cleave the lysosomal integral membrane protein type-2 (LIMP-2/SCARB2) required for normal biogenesis and maintenance of lysosomes and endosomes [138,139]; however, the exact mechanism by which CTSF deficiency translates in the clinical onset of CLN13 remains elusive. The biochemical and molecular mechanisms underlying NCLs have not been addressed yet.…”

Section: Gene Deficiency Biological Effect Referencesmentioning

confidence: 99%

Cathepsins in the Pathophysiology of Mucopolysaccharidoses: New Perspectives for Therapy

Pasquale

Moles

Pavone

2020

Cells

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Cathepsins (CTSs) are ubiquitously expressed proteases normally found in the endolysosomal compartment where they mediate protein degradation and turnover. However, CTSs are also found in the cytoplasm, nucleus, and extracellular matrix where they actively participate in cell signaling, protein processing, and trafficking through the plasma and nuclear membranes and between intracellular organelles. Dysregulation in CTS expression and/or activity disrupts cellular homeostasis, thus contributing to many human diseases, including inflammatory and cardiovascular diseases, neurodegenerative disorders, diabetes, obesity, cancer, kidney dysfunction, and others. This review aimed to highlight the involvement of CTSs in inherited lysosomal storage disorders, with a primary focus to the emerging evidence on the role of CTSs in the pathophysiology of Mucopolysaccharidoses (MPSs). These latter diseases are characterized by severe neurological, skeletal and cardiovascular phenotypes, and no effective cure exists to date. The advance in the knowledge of the molecular mechanisms underlying the activity of CTSs in MPSs may open a new challenge for the development of novel therapeutic approaches for the cure of such intractable diseases.

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“…Previous studies demonstrated that missense mutations in the CTSF gene caused Type B Kufs disease. Patients showed progressive neurodegeneration and accumulation of abnormal lipopigments in the brain and presented dementia and motor disturbances (Peters et al, 2015; Smith et al, 2013). However, disease mechanisms linking mutations in the CTSF gene to neurodegeneration and intralysosomal storage are still unclear.…”

Section: Discussionmentioning

confidence: 99%

“…However, CTSF expression levels were higher in several human cancer cell lines than in normal cells (Vazquez-Ortiz et al, 2005) suggesting that CTSF could play an important role in carcinogenesis. Moreover, previous studies have shown that mutations in the CTSF gene are associated with Type B Kufs disease, an adult form of neuronal ceroid lipofuscinosis (Peters et al, 2015; Smith et al, 2013). The present study aimed to identify and characterize the Alu -derived exonization events in the CTSF gene of the rhesus monkey ( Macaca mulatta ) and the crab-eating monkey ( Macaca fascicularis ).…”

Section: Introductionmentioning

confidence: 99%

Alu-Derived Alternative Splicing Events Specific to Macaca Lineages in CTSF Gene

Lee

Park

Kim

et al. 2017

Molecules and Cells

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Cathepsin F, which is encoded by CTSF, is a cysteine proteinase ubiquitously expressed in several tissues. In a previous study, novel transcripts of the CTSF gene were identified in the crab-eating monkey deriving from the integration of an Alu element–AluYRa1. The occurrence of AluYRa1-derived alternative transcripts and the mechanism of exonization events in the CTSF gene of human, rhesus monkey, and crab-eating monkey were investigated using PCR and reverse transcription PCR on the genomic DNA and cDNA isolated from several tissues. Results demonstrated that AluYRa1 was only integrated into the genome of Macaca species and this lineage-specific integration led to exonization events by producing a conserved 3′ splice site. Six transcript variants (V1–V6) were generated by alternative splicing (AS) events, including intron retention and alternative 5′ splice sites in the 5′ and 3′ flanking regions of CTSF_AluYRa1. Among them, V3–V5 transcripts were ubiquitously expressed in all tissues of rhesus monkey and crab-eating monkey, whereas AluYRa1-exonized V1 was dominantly expressed in the testis of the crab-eating monkey, and V2 was only expressed in the testis of the two monkeys. These five transcript variants also had different amino acid sequences in the C-terminal region of CTSF, as compared to reference sequences. Thus, species-specific Alu-derived exonization by lineage-specific integration of Alu elements and AS events seems to have played an important role during primate evolution by producing transcript variants and gene diversification.

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Lysosomal integral membrane protein type-2 (LIMP-2/SCARB2) is a substrate of cathepsin-F, a cysteine protease mutated in type-B-Kufs-disease

Cited by 14 publications

References 39 publications

Physical resistance training-induced changes in lipids metabolism pathways and apoptosis in prostate

Physical resistance training-induced changes in lipids metabolism pathways and apoptosis in prostate

Cathepsins in the Pathophysiology of Mucopolysaccharidoses: New Perspectives for Therapy

Alu-Derived Alternative Splicing Events Specific to Macaca Lineages in CTSF Gene

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