LIVIVO - Search results -

Search results

Result 1 - 10 of total 15

Search options

Article ; Online: PINK1 Protects against Staurosporine-Induced Apoptosis by Interacting with Beclin1 and Impairing Its Pro-Apoptotic Cleavage.

Brunelli, Francesco / Torosantucci, Liliana / Gelmetti, Vania / Franzone, Davide / Grünewald, Anne / Krüger, Rejko / Arena, Giuseppe / Valente, Enza Maria

Cells

2022 Volume 11, Issue 4

Abstract: ... ...

Abstract	PINK1
MeSH term(s)	Apoptosis ; Beclin-1/metabolism ; Humans ; Parkinson Disease ; Protein Kinases/metabolism ; Staurosporine/pharmacology
Chemical Substances	BECN1 protein, human ; Beclin-1 ; Protein Kinases (EC 2.7.-) ; PTEN-induced putative kinase (EC 2.7.11.1) ; Staurosporine (H88EPA0A3N)
Language	English
Publishing date	2022-02-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11040678
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: Candidate genes for Parkinson disease: Lessons from pathogenesis.

De Rosa, Priscilla / Marini, Elettra Sara / Gelmetti, Vania / Valente, Enza Maria

Clinica chimica acta; international journal of clinical chemistry

2015 Volume 449, Page(s) 68–76

Abstract: Parkinson disease (PD) is a multifactorial neurodegenerative disease characterized by the progressive loss of specific neuronal populations and accumulation of Lewy bodies in the brain, leading to motor and non-motor symptoms. In a small subset of ... ...

Abstract	Parkinson disease (PD) is a multifactorial neurodegenerative disease characterized by the progressive loss of specific neuronal populations and accumulation of Lewy bodies in the brain, leading to motor and non-motor symptoms. In a small subset of patients, PD is dominantly or recessively inherited, while a number of susceptibility genetic loci have been identified through genome wide association studies. The discovery of genes mutated in PD and functional studies on their protein products have provided new insights into the molecular events leading to neurodegeneration, suggesting that few interconnected molecular pathways may be deranged in all forms of PD, triggering neuronal loss. Here, we summarize the most relevant findings implicating the main PD-related proteins in biological processes such as mitochondrial dysfunction, misfolded protein damage, alteration of cellular clearance systems, abnormal calcium handling and altered inflammatory response, which represent key targets for neuroprotection.
MeSH term(s)	Autophagy/genetics ; Genetic Association Studies/methods ; Genetic Predisposition to Disease/genetics ; Genome-Wide Association Study/methods ; Humans ; Parkinson Disease/diagnosis ; Parkinson Disease/genetics
Language	English
Publishing date	2015-06-03
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80228-1
ISSN	1873-3492 ; 0009-8981
ISSN (online)	1873-3492
ISSN	0009-8981
DOI	10.1016/j.cca.2015.04.042
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ud II Zs.173: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Molecular pathways in sporadic PD.

Valente, Enza Maria / Arena, Giuseppe / Torosantucci, Liliana / Gelmetti, Vania

Parkinsonism & related disorders

2012 Volume 18 Suppl 1, Page(s) S71–3

Abstract: Over the last decade, several autosomal dominant and recessive genes causative of Parkinson's disease (PD) have been identified. The functional studies on their protein products and the pathogenetic effect related to their mutations have greatly ... ...

Abstract	Over the last decade, several autosomal dominant and recessive genes causative of Parkinson's disease (PD) have been identified. The functional studies on their protein products and the pathogenetic effect related to their mutations have greatly contributed to understand the many cellular pathways leading to neurodegeneration, that include oxidative stress damage, mitochondrial dysfunction, misfolded protein stress and impairment of cellular clearance systems, namely the ubiquitin-proteasome system (UPS) and the autophagy pathway. Although mendelian genes are responsible only for a small subset of PD patients, it is expected that the same pathogenetic mechanisms could play a relevant role also in the more frequent sporadic PD, that is currently recognized as a multifactorial disorder. In this model, different genetic and environmental factors, either playing a protective or a susceptibility role, variably interact to reach a threshold of disease over which PD will become clinically manifest. As an example, mutations or multiplication of the alpha-synuclein gene cause autosomal dominant PD, while common genetic variants at the same locus have been consistently associated to the risk of developing PD by genome-wide association studies. These findings are opening novel interesting perspectives to identify critical molecular pathways leading to neurodegeneration.
MeSH term(s)	Animals ; Genetic Variation/genetics ; Humans ; Neural Pathways/enzymology ; Neural Pathways/metabolism ; Parkinson Disease/enzymology ; Parkinson Disease/genetics ; Parkinson Disease/pathology ; Signal Transduction/genetics ; Ubiquitin-Protein Ligases/genetics ; alpha-Synuclein/genetics
Chemical Substances	alpha-Synuclein ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2012-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1311489-x
ISSN	1873-5126 ; 1353-8020
ISSN (online)	1873-5126
ISSN	1353-8020
DOI	10.1016/S1353-8020(11)70023-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4553: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 420: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: PINK1 and BECN1 relocalize at mitochondria-associated membranes during mitophagy and promote ER-mitochondria tethering and autophagosome formation.

Gelmetti, Vania / De Rosa, Priscilla / Torosantucci, Liliana / Marini, Elettra Sara / Romagnoli, Alessandra / Di Rienzo, Martina / Arena, Giuseppe / Vignone, Domenico / Fimia, Gian Maria / Valente, Enza Maria

Autophagy

2017 Volume 13, Issue 4, Page(s) 654–669

Abstract: Mitophagy is a highly specialized process to remove dysfunctional or superfluous mitochondria through the macroautophagy/autophagy pathway, aimed at protecting cells from the damage of disordered mitochondrial metabolism and apoptosis induction. PINK1, a ...

Abstract	Mitophagy is a highly specialized process to remove dysfunctional or superfluous mitochondria through the macroautophagy/autophagy pathway, aimed at protecting cells from the damage of disordered mitochondrial metabolism and apoptosis induction. PINK1, a neuroprotective protein mutated in autosomal recessive Parkinson disease, has been implicated in the activation of mitophagy by selectively accumulating on depolarized mitochondria, and promoting PARK2/Parkin translocation to them. While these steps have been characterized in depth, less is known about the process and site of autophagosome formation upon mitophagic stimuli. A previous study reported that, in starvation-induced autophagy, the proautophagic protein BECN1/Beclin1 (which we previously showed to interact with PINK1) relocalizes at specific regions of contact between the endoplasmic reticulum (ER) and mitochondria called mitochondria-associated membranes (MAM), from which the autophagosome originates. Here we show that, following mitophagic stimuli, autophagosomes also form at MAM; moreover, endogenous PINK1 and BECN1 were both found to relocalize at MAM, where they promoted the enhancement of ER-mitochondria contact sites and the formation of omegasomes, that represent autophagosome precursors. PARK2 was also enhanced at MAM following mitophagy induction. However, PINK1 silencing impaired BECN1 enrichment at MAM independently of PARK2, suggesting a novel role for PINK1 in regulating mitophagy. MAM have been recently implicated in many key cellular events. In this light, the observed prevalent localization of PINK1 at MAM may well explain other neuroprotective activities of this protein, such as modulation of mitochondrial calcium levels, mitochondrial dynamics, and apoptosis.
Language	English
Publishing date	2017-04-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2454135-7
ISSN	1554-8635 ; 1554-8627
ISSN (online)	1554-8635
ISSN	1554-8627
DOI	10.1080/15548627.2016.1277309
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 6741: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis.

Fazi, Francesco / Rosa, Alessandro / Fatica, Alessandro / Gelmetti, Vania / De Marchis, Maria Laura / Nervi, Clara / Bozzoni, Irene

Cell

2005 Volume 123, Issue 5, Page(s) 819–831

Abstract: MicroRNAs play important roles in cell differentiation by acting as translational inhibitors of specific target genes. Here we show that human granulocytic differentiation is controlled by a regulatory circuitry involving miR-223 and two transcriptional ... ...

Abstract	MicroRNAs play important roles in cell differentiation by acting as translational inhibitors of specific target genes. Here we show that human granulocytic differentiation is controlled by a regulatory circuitry involving miR-223 and two transcriptional factors, NFI-A and C/EBPalpha. The two factors compete for binding to the miR-223 promoter: NFI-A maintains miR-223 at low levels, whereas its replacement by C/EBPalpha, following retinoic acid (RA)-induced differentiation, upregulates miR-223 expression. The competition by C/EBPalpha and the granulocytic differentiation are favored by a negative-feedback loop in which miR-223 represses NFI-A translation. In line with this, both RNAi against NFI-A and ectopic expression of miR-223 in acute promyelocytic leukemia (APL) cells enhance differentiation, whereas miR-223 knockdown inhibits the differentiation response to RA. Altogether, our data indicate that miR-223 plays a crucial role during granulopoiesis and point to the NFI-A repression as an important molecular pathway mediating gene reprogramming in this cell lineage.
MeSH term(s)	Binding Sites ; CCAAT-Enhancer-Binding Protein-alpha/genetics ; CCAAT-Enhancer-Binding Protein-alpha/metabolism ; Cell Differentiation/physiology ; Cell Line ; Cell Lineage ; Gene Expression Regulation ; Granulocytes/drug effects ; Granulocytes/physiology ; Humans ; MicroRNAs ; Models, Biological ; Myelopoiesis/physiology ; NFI Transcription Factors/genetics ; NFI Transcription Factors/metabolism ; Promoter Regions, Genetic ; RNA Interference ; Tretinoin/pharmacology
Chemical Substances	CCAAT-Enhancer-Binding Protein-alpha ; MicroRNAs ; NFI Transcription Factors ; Tretinoin (5688UTC01R)
Language	English
Publishing date	2005-12-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2005.09.023
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1167: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 58: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Molecular signature of retinoic acid treatment in acute promyelocytic leukemia.

Meani, Natalia / Minardi, Simone / Licciulli, Silvia / Gelmetti, Vania / Coco, Francesco Lo / Nervi, Clara / Pelicci, Pier Giuseppe / Müller, Heiko / Alcalay, Myriam

Oncogene

2005 Volume 24, Issue 20, Page(s) 3358–3368

Abstract: Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia characterized by a block of differentiation at the promyelocytic stage. APL patients respond to pharmacological concentrations of all-trans retinoic acid (RA) and disease ... ...

Abstract	Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia characterized by a block of differentiation at the promyelocytic stage. APL patients respond to pharmacological concentrations of all-trans retinoic acid (RA) and disease remission correlates with terminal differentiation of leukemic blasts. The PML/RAR oncogenic transcription factor is responsible for both the pathogenesis of APL and for its sensitivity to RA. In order to identify physiological targets of RA therapy, we analysed gene expression profiles of RA-treated APL blasts and found 1056 common target genes. Comparing these results to those obtained in RA-treated U937 cell lines revealed that transcriptional response to RA is largely dependent on the expression of PML/RAR. Several genes involved in the control of differentiation and stem cell renewal are early targets of RA regulation, and may be important effectors of RA response. Modulation of chromatin modifying genes was also observed, suggesting that specific structural changes in local chromatin domains may be required to promote RA-mediated differentiation. Computational analysis of upstream genomic regions in RA target genes revealed nonrandom distribution of transcription factor binding sites, indicating that specific transcriptional regulatory complexes may be involved in determining RA response.
MeSH term(s)	Binding Sites ; Cell Line, Tumor ; Chromatin/metabolism ; Cluster Analysis ; Exons ; Gene Expression Regulation, Neoplastic ; Humans ; Leukemia, Promyelocytic, Acute/drug therapy ; Leukemia, Promyelocytic, Acute/genetics ; Leukemia, Promyelocytic, Acute/metabolism ; Oligonucleotide Array Sequence Analysis ; Promoter Regions, Genetic ; Protein Structure, Tertiary ; RNA/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription Factors/metabolism ; Transcription, Genetic ; Tretinoin/metabolism ; Tretinoin/pharmacology ; Tumor Cells, Cultured ; U937 Cells
Chemical Substances	Chromatin ; Transcription Factors ; Tretinoin (5688UTC01R) ; RNA (63231-63-0)
Language	English
Publishing date	2005-05-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639046-8
ISSN	1476-5594 ; 0950-9232
ISSN (online)	1476-5594
ISSN	0950-9232
DOI	10.1038/sj.onc.1208498
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2218: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Targeting fusion protein/corepressor contact restores differentiation response in leukemia cells.

Racanicchi, Serena / Maccherani, Chiara / Liberatore, Concetta / Billi, Monia / Gelmetti, Vania / Panigada, Maddalena / Rizzo, Giovanni / Nervi, Clara / Grignani, Francesco

The EMBO journal

2005 Volume 24, Issue 6, Page(s) 1232–1242

Abstract: The AML1/ETO and PML/RARalpha leukemia fusion proteins induce acute myeloid leukemia by acting as transcriptional repressors. They interact with corepressors, such as N-CoR and SMRT, that recruit a multiprotein complex containing histone deacetylases on ... ...

Abstract	The AML1/ETO and PML/RARalpha leukemia fusion proteins induce acute myeloid leukemia by acting as transcriptional repressors. They interact with corepressors, such as N-CoR and SMRT, that recruit a multiprotein complex containing histone deacetylases on crucial myeloid differentiation genes. This leads to gene repression contributing to generate a differentiation block. We expressed in leukemia cells containing PML/RARalpha and AML1/ETO N-CoR protein fragments derived from fusion protein/corepressor interaction surfaces. This blocks N-CoR/SMRT binding by these fusion proteins, and disrupts the repressor protein complex. In consequence, the expression of genes repressed by these fusion proteins increases and differentiation response to vitamin D3 and retinoic acid is restored in previously resistant cells. The alteration of PML/RARalpha-N-CoR/SMRT connections triggers proteasomal degradation of the fusion protein. The N-CoR fragments are biologically effective also when directly transduced by virtue of a protein transduction domain. Our data indicate that fusion protein activity is permanently required to maintain the leukemia phenotype and show the route to developing a novel therapeutic approach for leukemia, based on its molecular pathogenesis.
MeSH term(s)	Acute Disease ; Cell Differentiation/drug effects ; Cell Line, Tumor ; Cholecalciferol/pharmacology ; Core Binding Factor Alpha 2 Subunit ; DNA-Binding Proteins/antagonists & inhibitors ; DNA-Binding Proteins/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Leukemia, Myeloid/metabolism ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Nuclear Proteins/antagonists & inhibitors ; Nuclear Proteins/metabolism ; Nuclear Receptor Co-Repressor 1 ; Nuclear Receptor Co-Repressor 2 ; Oncogene Proteins, Fusion/genetics ; Oncogene Proteins, Fusion/metabolism ; Peptides/genetics ; Peptides/physiology ; Protein Structure, Tertiary/genetics ; Protein Structure, Tertiary/physiology ; RUNX1 Translocation Partner 1 Protein ; Repressor Proteins/antagonists & inhibitors ; Repressor Proteins/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Tretinoin/pharmacology
Chemical Substances	AML1-ETO fusion protein, human ; Core Binding Factor Alpha 2 Subunit ; DNA-Binding Proteins ; NCOR1 protein, human ; NCOR2 protein, human ; Neoplasm Proteins ; Nuclear Proteins ; Nuclear Receptor Co-Repressor 1 ; Nuclear Receptor Co-Repressor 2 ; Oncogene Proteins, Fusion ; Peptides ; RUNX1 Translocation Partner 1 Protein ; Repressor Proteins ; Transcription Factors ; promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein ; Cholecalciferol (1C6V77QF41) ; Tretinoin (5688UTC01R)
Language	English
Publishing date	2005-03-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	586044-1
ISSN	1460-2075 ; 0261-4189
ISSN (online)	1460-2075
ISSN	0261-4189
DOI	10.1038/sj.emboj.7600593
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1808: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 100: Show issues

Order via subito

Details ▾

Article ; Online: A variant in the carboxyl-terminus of connexin 40 alters GAP junctions and increases risk for tetralogy of Fallot.

Guida, Valentina / Ferese, Rosangela / Rocchetti, Marcella / Bonetti, Monica / Sarkozy, Anna / Cecchetti, Serena / Gelmetti, Vania / Lepri, Francesca / Copetti, Massimiliano / Lamorte, Giuseppe / Cristina Digilio, Maria / Marino, Bruno / Zaza, Antonio / den Hertog, Jeroen / Dallapiccola, Bruno / De Luca, Alessandro

European journal of human genetics : EJHG

2012 Volume 21, Issue 1, Page(s) 69–75

Abstract: GJA5 gene (MIM no. 121013), localized at 1q21.1, encodes for the cardiac gap junction protein connexin 40. In humans, copy number variants of chromosome 1q21.1 have been associated with variable phenotypes comprising congenital heart disease (CHD), ... ...

Abstract	GJA5 gene (MIM no. 121013), localized at 1q21.1, encodes for the cardiac gap junction protein connexin 40. In humans, copy number variants of chromosome 1q21.1 have been associated with variable phenotypes comprising congenital heart disease (CHD), including isolated TOF. In mice, the deletion of Gja5 can cause a variety of complex CHDs, in particular of the cardiac outflow tract, corresponding to TOF in many cases. In the present study, we screened for mutations in the GJA5 gene 178 unrelated probands with isolated TOF. A heterozygous nucleotide change (c.793C>T) in exon 2 of the gene leading to the p.Pro265Ser variant at the carboxyl-terminus of the protein was found in two unrelated sporadic patients, one with classic anatomy and one with pulmonary atresia. This GJA5 missense substitution was not observed in 1568 ethnically-matched control chromosomes. Immunofluorescent staining and confocal microscopy revealed that cells expressing the mutant protein form sparse or no visible gap-junction plaques in the region of cell-cell contact. Moreover, analysis of the transfer of the gap junction permanent tracer lucifer yellow showed that cells expressing the mutant protein have a reduced rate of dye transfer compared with wild-type cells. Finally, use of a zebrafish model revealed that microinjection of the GJA5-p.Pro265Ser mutant disrupts overall morphology of the heart tube in the 37% (22/60) of embryos, compared with the 6% (4/66) of the GJA5 wild-type-injected embryos. These findings implicate GJA5 gene as a novel susceptibility gene for TOF.
MeSH term(s)	Amino Acid Substitution ; Animals ; Chromosomes, Human, Pair 1 ; Connexins/genetics ; Connexins/metabolism ; Embryo, Nonmammalian/pathology ; Fluorescent Dyes/metabolism ; Gap Junctions/metabolism ; Genetic Predisposition to Disease ; Heart/embryology ; Heterozygote ; Humans ; Microinjections ; Mutation ; Mutation, Missense ; Myocardium/pathology ; Pulmonary Atresia/genetics ; Tetralogy of Fallot/genetics ; Zebrafish/genetics ; Gap Junction alpha-5 Protein
Chemical Substances	Connexins ; Fluorescent Dyes
Language	English
Publishing date	2012-06-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1141470-4
ISSN	1476-5438 ; 1018-4813
ISSN (online)	1476-5438
ISSN	1018-4813
DOI	10.1038/ejhg.2012.109
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 3589: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Late onset sporadic Parkinson's disease caused by PINK1 mutations: clinical and functional study.

Gelmetti, Vania / Ferraris, Alessandro / Brusa, Livia / Romano, Francesca / Lombardi, Federica / Barzaghi, Chiara / Stanzione, Paolo / Garavaglia, Barbara / Dallapiccola, Bruno / Valente, Enza Maria

Movement disorders : official journal of the Movement Disorder Society

2008 Volume 23, Issue 6, Page(s) 881–885

Abstract: Homozygous or compound heterozygous mutations in the PINK1 gene represent the second most frequent cause of autosomal recessive parkinsonism after Parkin. The phenotype differs from idiopathic Parkinson's disease for earlier onset, slower disease ... ...

Abstract	Homozygous or compound heterozygous mutations in the PINK1 gene represent the second most frequent cause of autosomal recessive parkinsonism after Parkin. The phenotype differs from idiopathic Parkinson's disease for earlier onset, slower disease progression, and better response to therapy. Indeed, the rare patients with onset above 50 years are usually relatives of early-onset probands. Here, we report the first occurrence of compound heterozygous PINK1 mutations in a sporadic patient with a phenotype indistinguishable from idiopathic Parkinson's disease (PD), with onset in the late seventh decade, rapid progression and good response to levodopa that waned with time. Both mutations (p.A244G and p.V317I) were found to abolish the protective effect of wild-type PINK1 against staurosporine-induced apoptosis. These findings further expand the clinical spectrum of PINK1-related parkinsonism to include late onset, typical PD, and underline the existing difficulties in discriminating between mendelian parkinsonism and idiopathic PD.
MeSH term(s)	Aged ; Female ; Humans ; Male ; Middle Aged ; Mutagenesis, Site-Directed ; Mutation ; Parkinsonian Disorders/genetics ; Protein Kinases/genetics ; Staurosporine/pharmacology ; Transfection ; Ubiquitin-Protein Ligases/genetics
Chemical Substances	Ubiquitin-Protein Ligases (EC 2.3.2.27) ; parkin protein (EC 2.3.2.27) ; Protein Kinases (EC 2.7.-) ; PTEN-induced putative kinase (EC 2.7.11.1) ; Staurosporine (H88EPA0A3N)
Language	English
Publishing date	2008-02-29
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	607633-6
ISSN	1531-8257 ; 0885-3185
ISSN (online)	1531-8257
ISSN	0885-3185
DOI	10.1002/mds.21960
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2555: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 238: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Heterochromatic gene repression of the retinoic acid pathway in acute myeloid leukemia.

Fazi, Francesco / Zardo, Giuseppe / Gelmetti, Vania / Travaglini, Lorena / Ciolfi, Alberto / Di Croce, Luciano / Rosa, Alessandro / Bozzoni, Irene / Grignani, Francesco / Lo-Coco, Francesco / Pelicci, Pier Giuseppe / Nervi, Clara

Blood

2007 Volume 109, Issue 10, Page(s) 4432–4440

Abstract: Alteration of lineage-specific transcriptional programs for hematopoiesis causes differentiation block and promotes leukemia development. Here, we show that AML1/ETO, the most common translocation fusion product in acute myeloid leukemia (AML), ... ...

Abstract	Alteration of lineage-specific transcriptional programs for hematopoiesis causes differentiation block and promotes leukemia development. Here, we show that AML1/ETO, the most common translocation fusion product in acute myeloid leukemia (AML), counteracts the activity of retinoic acid (RA), a transcriptional regulator of myelopoiesis. AML1/ETO participates in a protein complex with the RA receptor alpha (RARalpha) at RA regulatory regions on RARbeta2, which is a key RA target gene mediating RA activity/resistance in cells. At these sites, AML1/ETO recruits histone deacetylase, DNA methyltransferase, and DNA-methyl-CpG binding activities that promote a repressed chromatin conformation. The link among AML1/ETO, heterochromatic RARbeta2 repression, RA resistance, and myeloid differentiation block is indicated by the ability of either siRNA-AML1/ETO or the DNA methylation inhibitor 5-azacytidine to revert these epigenetic alterations and to restore RA differentiation response in AML1/ETO blasts. Finally, RARbeta2 is commonly silenced by hypermethylation in primary AML blasts but not in normal hematopoietic precursors, thus suggesting a role for the epigenetic repression of the RA signaling pathway in myeloid leukemogenesis.
MeSH term(s)	Acute Disease ; Cell Differentiation/drug effects ; Cell Differentiation/genetics ; Cells, Cultured ; Core Binding Factor Alpha 2 Subunit/antagonists & inhibitors ; Core Binding Factor Alpha 2 Subunit/genetics ; Core Binding Factor Alpha 2 Subunit/metabolism ; Core Binding Factor Alpha 2 Subunit/physiology ; Gene Expression Regulation, Leukemic/drug effects ; Gene Silencing ; Heterochromatin/physiology ; Humans ; Leukemia, Myeloid/genetics ; Leukemia, Myeloid/metabolism ; Leukemia, Myeloid/pathology ; Oncogene Proteins, Fusion/antagonists & inhibitors ; Oncogene Proteins, Fusion/genetics ; Oncogene Proteins, Fusion/metabolism ; Oncogene Proteins, Fusion/physiology ; Protein Binding ; RUNX1 Translocation Partner 1 Protein ; Receptors, Retinoic Acid/genetics ; Receptors, Retinoic Acid/metabolism ; Response Elements ; Retinoid X Receptors/metabolism ; Signal Transduction/genetics ; Transfection ; Tretinoin/metabolism ; Tretinoin/pharmacology ; U937 Cells
Chemical Substances	AML1-ETO fusion protein, human ; Core Binding Factor Alpha 2 Subunit ; Heterochromatin ; Oncogene Proteins, Fusion ; RUNX1 Translocation Partner 1 Protein ; Receptors, Retinoic Acid ; Retinoid X Receptors ; Tretinoin (5688UTC01R)
Language	English
Publishing date	2007-01-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2006-09-045781
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uh III Zs.140: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 364: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito