6533b860fe1ef96bd12c316e
RESEARCH PRODUCT
The prolyl-isomerase PIN1 is essential for nuclear Lamin-B structure and function and protects heterochromatin under mechanical stress.
Valentina FajnerAlessandra RustighiAlessandra RustighiIlaria Anna Pia VotoValeria SpecchiaStefano GustincichStefano GustincichClara DeziElena ValentinoValeria CancilaFabrizio D'adda Di FagagnaElena MasperoRemo SangesFrancesco NapoletanoFrancesco NapoletanoElena CampanerElena CampanerClaudio TripodoSara FinauriniAntonello MallamaciFederico AnsaloniGloria Ferrari BravoGloria Ferrari BravoArianna BertossiArianna BertossiFiamma MantovaniFiamma MantovaniLucia CeloraMariangela SantorsolaMariangela SantorsolaManuela SantoGiannino Del SalGiannino Del SalUbaldo GioiaOsvaldo Basilio ArtimagnellaSimona PoloAurora SantinCesare Valentisubject
transposonsNeocortexMiceHeterochromatinProlyl isomeraseDrosophila ProteinsBiology (General)PhosphorylationRNA Small InterferingTissue homeostasisCells CulturedSettore ING-INF/05 - Sistemi Di Elaborazione Delle InformazioniNeuronsLamin Type BChemistryHP1phosphorylationneurodegenerationnuclear envelopePeptidylprolyl IsomeraseCell biologyDrosophila heterochromatin HP1 Lamin mechanical stress neurodegeneration nuclear envelope phosphorylation PIN1 transposonsNuclear laminaDrosophilaRNA InterferencePremature agingQH301-705.5HeterochromatinNuclear EnvelopeDrosophila; heterochromatin; HP1; Lamin; mechanical stress; neurodegeneration; nuclear envelope; phosphorylation; PIN1; transposonsSettore BIO/11 - Biologia MolecolareSettore MED/08 - Anatomia PatologicaGeneral Biochemistry Genetics and Molecular BiologyPIN1Alzheimer DiseaseSettore MED/05 - Patologia ClinicaAnimalsHumansHeterochromatin maintenancemechanical stressheterochromatinmechanical streMice Inbred C57BLNIMA-Interacting Peptidylprolyl IsomeraseChromobox Protein Homolog 5DNA Transposable ElementsHeterochromatin protein 1Stress MechanicalLaminLamindescription
Summary: Chromatin organization plays a crucial role in tissue homeostasis. Heterochromatin relaxation and consequent unscheduled mobilization of transposable elements (TEs) are emerging as key contributors of aging and aging-related pathologies, including Alzheimer’s disease (AD) and cancer. However, the mechanisms governing heterochromatin maintenance or its relaxation in pathological conditions remain poorly understood. Here we show that PIN1, the only phosphorylation-specific cis/trans prolyl isomerase, whose loss is associated with premature aging and AD, is essential to preserve heterochromatin. We demonstrate that this PIN1 function is conserved from Drosophila to humans and prevents TE mobilization-dependent neurodegeneration and cognitive defects. Mechanistically, PIN1 maintains nuclear type-B Lamin structure and anchoring function for heterochromatin protein 1α (HP1α). This mechanism prevents nuclear envelope alterations and heterochromatin relaxation under mechanical stress, which is a key contributor to aging-related pathologies.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-09-01 | Cell reports |