A5085080438- Ubiquitin and proteasome pathways
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Multiple Myeloma Research and Treatments
- Immune Cell Function and Interaction
- Renal Diseases and Glomerulopathies
- Cytokine Signaling Pathways and Interactions
- Legal and Labor Studies
- Immune cells in cancer
- Renin-Angiotensin System Studies
- T-cell and B-cell Immunology
- interferon and immune responses
- Renal and Vascular Pathologies
- Nitric Oxide and Endothelin Effects
- Peptidase Inhibition and Analysis
- Protein Degradation and Inhibitors
- Amino Acid Enzymes and Metabolism
- Kidney Stones and Urolithiasis Treatments
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Phagocytosis and Immune Regulation
- Immunotoxicology and immune responses
- Chronic Kidney Disease and Diabetes
- Pancreatic function and diabetes
- Birth, Development, and Health
- Caveolin-1 and cellular processes
IRCCS Ospedale San Raffaele
2022-2024
University of Padua
2024
Beth Israel Deaconess Medical Center
2022
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2017-2021
Vita-Salute San Raffaele University
2004-2021
Istituti di Ricovero e Cura a Carattere Scientifico
2017-2021
San Raffaele University of Rome
1999-2009
Mario Negri Institute for Pharmacological Research
1983-1985
Centro Ricerche FIAT
1983
Many proteins of the secretory pathway contain disulfide bonds that are essential for structure and function. In endoplasmic reticulum (ER), Ero1 alpha beta oxidize protein isomerase (PDI), which in turn transfers oxidative equivalents to newly synthesized cargo proteins. However, oxidation must be limited, as some reduced PDI is necessary isomerization ER-associated degradation. Here we show semipermeable cells, more oxidized, formed faster, high molecular mass covalent aggregates...
A previously unsuspected, considerable proportion of newly synthesized polypeptides are hydrolyzed rapidly by proteasomes, possibly competing with endogenous substrates and altering proteostasis. In view the anti-cancer effects PIs, we set out to achieve a quantitative assessment proteasome workload in cells hallmarked different PI sensitivity, namely, panel MM cells, dynamic model plasma cell differentiation, process that confers exquisite sensitivity. Our results suggest protein synthesis...
The kidney-specific gene UMOD encodes for uromodulin, the most abundant protein excreted in normal urine. Rare large-effect variants cause autosomal dominant tubulointerstitial kidney disease (ADTKD), while common low-impact strongly associate with function and risk of chronic (CKD) general population. It is unknown whether intermediate-effect contribute to CKD. Here, candidate were identified using large-population ADTKD cohorts. Biological phenotypical effects investigated cell models,...
Abstract Upon encounter with Ag, B lymphocytes undergo terminal differentiation into plasma cells, highly specialized Ab secretors that mediate humoral immune responses. Profound changes adapt cellular morphology and proteome to the new secretory functions. Although a massive activity is expected require an efficient ubiquitin‐proteasome degradation system, recent in vitro studies have surprisingly revealed proteasome function sharply decreases during cell development, thereby limiting...
Uromodulin is the most abundant urinary protein in physiological conditions. It exclusively produced by renal epithelial cells lining thick ascending limb of Henle's loop (TAL) and it plays key roles kidney function disease. Mutations UMOD, gene encoding uromodulin, cause autosomal dominant tubulointerstitial disease uromodulin-related (ADTKD-UMOD), characterised hyperuricemia, gout progressive loss function. While primary effect UMOD mutations, retention endoplasmic reticulum (ER), well...
FAM46C is a non-canonical poly(A) polymerase uniquely mutated in up to 20% of multiple myeloma (MM) patients, implying tissue-specific tumor suppressor function. Here, we report that selectively stabilizes mRNAs encoding endoplasmic reticulum (ER)-targeted proteins, thereby concertedly enhancing the expression proteins control ER protein import, folding, N-glycosylation, and trafficking boosting secretion. This role requires interaction with membrane resident FNDC3A FNDC3B. In MM cells,...
Abstract Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a genetically heterogeneous renal disorder leading to progressive loss of function. ADTKD- REN due rare mutations in renin, all localized the protein leader peptide and affecting its co-translational insertion endoplasmic reticulum (ER). Through exome sequencing an adult-onset ADTKD family we identified new renin variant, p.L381P, mapping mature protein. To assess pathogenicity, combined genetic data, computational...
Macrophages (M phi diameter) from three mouse strains with genetically distinct M diameter deficits (C3H/HeJ, A/J, and P/J) were unable to develop high cytolytic cytotoxic activity against tumor cells in vitro when exposed agents (MAF IFN-beta) that strongly increased the tumoricidal capacity of nondefective C3H/HeN mice. Nevertheless, defective did not affect their suppressive on Con A-induced lymphoproliferation, nor ability react IFN-beta by decreasing activity. In fact, natural...
Autosomal Dominant Tubulointerstitial Kidney Disease, a rare genetic disorder characterised by progressive chronic kidney disease, is caused mutations in different genes including REN, encoding renin. Renin secreted protease composed of 3 domains: the leader peptide allowing insertion endoplasmic reticulum (ER), pro-segment regulating its activity, and mature part. Mutations renin lead to ER retention mutant protein late onset while peptide, associated with defective translocation,...
Working mothers must often balance work and family responsibilities which can be affected by rigid irrational beliefs about motherhood. The present study had two aims: (a) to provide psychometric evidence for a shortened Italian version of the Rigid Maternal Beliefs Scale (RMBS) (b) facilitate mothers' return after maternity leave reducing perceptions anxiety stress related maternal (i.e., societal expectations mothers, confidence, dichotomy) teaching specific recovery strategies (e.g.,...
Abstract The kidney-specific gene UMOD encodes for uromodulin, the most abundant protein excreted in normal urine. Rare, large-effect variants cause autosomal dominant tubulointerstitial kidney disease (ADTKD) while common, low-effect strongly associate with function and risk of chronic (CKD) general population. It is unknown whether intermediate-effect contribute to CKD. Here, candidate were identified using large population ADTKD cohorts. Biological phenotypical effects investigated cell...