A5078641567- Autophagy in Disease and Therapy
- Calpain Protease Function and Regulation
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Toxoplasma gondii Research Studies
- HIV Research and Treatment
- Cell death mechanisms and regulation
- RNA regulation and disease
- Genomics and Chromatin Dynamics
- Peptidase Inhibition and Analysis
- NF-κB Signaling Pathways
- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Signaling Pathways in Disease
- Lipid metabolism and biosynthesis
- Phagocytosis and Immune Regulation
- HER2/EGFR in Cancer Research
- DNA and Nucleic Acid Chemistry
- Breast Cancer Treatment Studies
- Cancer-related gene regulation
- HIV/AIDS drug development and treatment
- Peroxisome Proliferator-Activated Receptors
- Wnt/β-catenin signaling in development and cancer
- RNA modifications and cancer
- Cannabis and Cannabinoid Research
Consorzio Interuniversitario per le Biotecnologie
2006-2021
Institut National du Cancer
2019
AREA Science Park
2012-2017
Washtenaw Community College
2012
University of Michigan
2012
UiT The Arctic University of Norway
2012
University of Cincinnati
2008
International Centre for Genetic Engineering and Biotechnology
1989-2004
Recently, autophagy has emerged as a critical process in the control of T-cell homeostasis. Given pivotal role NF-kappaB signaling events T cells, we have analyzed and unveiled conserved binding site promoter murine human BECN1 autophagic gene (Atg6). Accordingly, demonstrate that family member p65/RelA upregulates mRNA protein levels different cellular systems. Moreover, p65-mediated upregulation is coupled to increased autophagy. The newly identified kappaB specifically interacts with p65...
A number of different kinases have been implicated in NF-κB regulation and survival function. Here we investigated the molecular cross-talk between glycogen synthase kinase-3β (GSK-3β) p105 precursor p50 subunit. GSK-3β forms an vivo complex with specifically phosphorylates NF-κB1/p105 at Ser-903 Ser-907 vitro. In addition, phosphorylation level is reduced fibroblasts lacking as compared wild-type cells. has a dual effect on p105: it stabilizes under resting conditions primes for degradation...
Ubiquitously expressed micro- and millicalpain, which both require the calpain small 1 (CAPNS1) regulatory subunit for function, play important roles in numerous biological pathological phenomena. We have previously shown that product of GAS2, a gene specifically induced at growth arrest, is an inhibitor millicalpain its overexpression sensitizes cells to apoptosis p53-dependent manner (Benetti, R., G. Del Sal, M. Monte, Paroni, C. Brancolini, Schneider. 2001. EMBO J. 20:2702-2714). More...
A recombinant Tat protein was used to investigate the molecular mechanisms of transcriptional activation human immunodeficiency virus type 1 long terminal repeat (LTR). Liposome-mediated delivery this responsive cells results in dose-dependent LTR activation. As evaluated by mRNA quantitation with competitive PCR, response is rapid and transient, peaking at 5 h after beginning treatment. In vivo footprinting experiments showed that concomitant a modification protein-DNA interaction pattern...
Transcriptional interference between adjacent genes has been demonstrated in a variety of biological systems. To study this process RNA polymerase II (pol II) transcribed we have analysed the effect transcription on tandem HIV-1 promoters integrated into genome HeLa cells. We show that transcriptional activation at upstream promoter reduces from downstream promoter, as compared with basal conditions (in absence an activator). Furthermore, insertion strong termination element two alleviates...
ABSTRACT The transactivator protein of human immunodeficiency virus type 1 (HIV-1) (Tat) is a powerful activator nuclear factor-κB (NF-κB), acting through degradation the inhibitor IκB-α (F. Demarchi, F. d’Adda di Fagagna, A. Falaschi, and M. Giacca, J. Virol. 70:4427–4437, 1996). Here, we show that this activity Tat requires function cellular interferon-inducible kinase PKR. Tat-mediated NF-κB activation transcriptional induction HIV-1 long terminal repeat were impaired in murine cells...
The growth arrest-specific 6 gene product Gas6 is a and survival factor related to protein S. the ligand of Axl receptor tyrosine kinase; upon binding its activates phosphatidylinositol 3-OH kinase (PI3K) downstream targets S6K Akt. anti-apoptotic signaling was previously shown require functional PI3K Akt involve Bad phosphorylation in serum-starved NIH 3T3 cells. Here we demonstrate that induces rapid transient increase nuclear NF-κB activity coupled transcription activation from...
ULK1 (unc-51 like autophagy activating kinase 1) is a core component at multiple steps of canonical macroautophagy/autophagy. The activity tightly regulated by several post-translational modifications, including ubiquitination, yet the deubiquitinase (DUB) responsible for its reversible deubiquitination has not been described. Here, we identified USP1 (ubiquitin specific peptidase as key player in modulation K63-linked deubiquitination. Moreover, both depletion and chemical inhibition...
The regulation of the rate transcription human immunodeficiency virus type 1 is mainly exerted through long terminal repeat (LTR) at 5' end provirus. A large number cis-acting regulatory elements have been identified in LTR by vitro binding studies; biological role these sites within living infected cells, however, still not clear. We studied interactions nuclear proteins with U1 monocytic cell line vivo dimethylsulfate footprinting, using ligation-mediated polymerase chain reaction...
We unveiled novel p65/RelA consensus sites in the promoter of beclin 1 gene and demonstrate that positively modulates canonical autophagy various human cell lines both under basal conditions upon induction by ceramide. Interestingly, we find T receptor-dependent activation Jurkat cells triggers an increase binding to accompanied enhanced autophagy, suggesting could regulate T-cell homeostasis through autophagy.
Protein-DNA interactions were studied in vivo at the region containing a human DNA replication origin, located 3' end of lamin B2 gene and partially overlapping promoter another gene, downstream. DNase I treatment nuclei isolated from both exponentially growing nonproliferating HL-60 cells showed that this has an altered, highly accessible, chromatin structure. High-resolution analysis protein-DNA 600-bp area encompassing origin was carried out by footprinting technique based on...
Ubiquitously expressed mu- and m-calpain proteases consist of 80-kDa catalytic subunits encoded by the Capn1 Capn2 genes, respectively, a common 28-kDa regulatory subunit calpain small 1 (Capns1) gene.The have been implicated in both pro- or anti-apoptotic functions. We found that Capns1 depletion is coupled to increased sensitivity apoptosis triggered number autophagy-inducing stimuli mammalian cells. Therefore we investigated involvement calpains autophagy using MEFs derived from knockout...
Inhibitors of the ubiquitin-proteasome system (UPSIs) promote apoptosis cancer cells and show encouraging anti-tumor activities in vivo. In this study, we evaluated death two different UPSIs: bortezomib isopeptidase inhibitor G5. To unveil whether these compounds elicit types death, compared their effect both on apoptosis-proficient wild type mouse embryo fibroblasts defective for (double-deficient Bax/Bak fibroblasts) (double knockout; DKO). We have discovered that (i) inhibitors induce a...
Calpains regulate a wide spectrum of biological functions, including migration, adhesion, apoptosis, secretion, and autophagy, through the modulating cleavage specific substrates. Ubiquitous microcalpain (μ-calpain) millicalpain (m-calpain) are heterodimers composed catalytic subunits encoded, respectively, by CAPN1 CAPN2 regulatory subunit encoded CAPNS1. Here we show that calpain is required for stability deubiquitinating enzyme USP1 in several cell lines. modulates DNA replication...
The HMGA1 architectural transcription factor is an oncogene overexpressed in the vast majority of human cancers. a highly connected node nuclear molecular network and key aspect involvement cancer development that simultaneously confers cells multiple oncogenic hits, ranging from global chromatin structural gene expression modifications up to direct functional alterations cellular proteins. Interestingly, also modulates DNA damage repair pathways. In this work, we provide evidences linking...
AbstractSenescence represents an important barrier against cellular transformation. Here we show that CAPNS1 depletion impairs senescence induction both in BJ-ET H-Rasv12 inducible human fibroblasts upon Ras and HT1080 targeted to by treatment with low doses of doxorubicin. We further is coupled reduced levels H2AX phosphorylation, not only Rasv12 induced fibroblasts, but also a number systems genotoxic stress. In particular affects γ-H2AX appearance or persistence U2OS osteosarcoma cells 24...
CAPNS1 is essential for stability and function of the ubiquitous calcium dependent proteases micro- milli-calpain. Upon inhibition endoplasmic reticulum Ca2+ ATPase by 100nM thapsigargin, both micro-calpain autophagy are activated in human U2OS osteosarcoma cells a manner. As reported other triggers, thapsigargin treatment induces Golgi fragmentation fusion Atg9/Bif-1 containing vesicles with LC3 bodies control cells. On opposite, depletion coupled to an accumulation Rab5 early endosomes....
We have analyzed protein-DNA interactions at the long terminal repeat of human immunodeficiency virus type 1 in a productively infected T-cell line by vivo dimethyl sulfate footprinting. Major footprints are evident basal promoter and enhancer elements. In particular, proteins appear to occupy TATA box, Sp1 sites, two repeats region. negative regulatory element, protections detected over USF/MLTF NFAT-1 sites. Furthermore, previously unrecognized from nucleotides -260 -275 -205 -216,...