ANGELA KARIMPOUR GHAHNAVIEH

Dottoressa di ricerca

ciclo: XXXV


supervisore: Giansanti Maria Grazia
relatore: Giansanti Maria Grazia
co-supervisore: Cenci Giovanni

Titolo della tesi: Using Drosophila melanogaster to dissect the role of the oncoprotein GOLPH3 in cytokinesis and cellular growth

Golgi phosphoprotein 3 (GOLPH3) is a Phosphatidylinositol-4- phosphate [PI(4)P] binding Golgi protein required for Golgi architecture, vesicle trafficking and glycosylation. Overexpression of human GOLPH3 has been reported in several solid tumors and correlates with poor prognosis in breast cancer and glioblastoma multiforme. The oncogenic activity of GOLPH3 has been linked to enhanced signaling downstream of mechanistic target of rapamycin (mTOR), an evolutionarily conserved serine/threonine protein kinase However, the molecular pathways through which GOLPH3 acts in malignant transformation remain to be clarified. It has been suggested that GOLPH3 protein might prevent tumorigenesis by (i): regulating Golgi-to-plasma secretory trafficking of growth factors, (ii): controlling the recycling or glycosylation of cancer relevant glycoproteins. Moreover, research studies in Drosophila have involved GOLPH3 protein in cytokinesis. This is highly relevant in GOLPH3 cancer biology because cytokinesis failures lead to ploidy increase, which in turn promotes chromosome instability, tumorigenesis and resistance to anti-cancer therapy. My PhD studies have been focused on the analysis of the cellular functions of GOLPH3 protein and its molecular partners using Drosophila melanogaster as a model organism. In the first chapter I investigate the role of Drosophila GOLPH3 (dGOLPH3) during the early steps of cytokinesis. dGOLPH3 accumulates at the cleavage furrow of dividing cells and interacts with the cytokinetic machinery and vesicle trafficking proteins. I demonstrate that GOLPH3 cooperates with non-muscle myosin II to regulate centralspindlin stabilization and contractile ring structure at the cleavage site. In the second chapter I use affinity purification coupled with mass spectrometry to identify the protein-protein interaction network (interactome) of Drosophila GOLPH3 in testes. Consistent with previous findings that dGOLPH3 controls membrane trafficking during cytokinesis, the dGOLPH3 interactome revealed an enrichment of proteins involved in cell cycle regulation and vesicle-mediated trafficking. In the last chapter I demonstrate that dGOLPH3 is required for tissue growth in Drosophila by regulating Rheb-mediated mTOR activation. Overall, my results shed light on the mechanisms underlying the role of GOLPH3 in cellular transformation and suggest possible therapeutic intervention for tumor pathologies characterized by GOLPH3 upregulation.  

Produzione scientifica

  • 11573/1334563 - 2019 - Drosophila doublefault protein coordinates multiple events during male meiosis by controlling mRNA translation (01a Articolo in rivista)
    FRAPPAOLO, ANNA; KARIMPOUR GHAHNAVIEH, ANGELA; GOTTARDO, MARIA GIUSEPPINA; BURLA, ROMINA; SCHININA', MARIA EUGENIA; SAGGIO, ISABELLA
  • 11573/1394194 - 2017 - COG7 deficiency in Drosophila generates multifaceted developmental, behavioral and protein glycosylation phenotypes (01a Articolo in rivista)
    KARIMPOUR GHAHNAVIEH, ANGELA; BELLONI, GIORGIO; PIERGENTILI, ROBERTO
  • 11573/1496160 - 2020 - The close relationship between the Golgi trafficking machinery and protein glycosylation (01g Articolo di rassegna (Review))
    FRAPPAOLO, ANNA; KARIMPOUR GHAHNAVIEH, ANGELA; SECHI, STEFANO
  • 11573/1573796 - 2021 - Identification of GOLPH3 partners in Drosophila unveils potential novel roles in tumorigenesis and neural disorders (01a Articolo in rivista)
    KARIMPOUR GHAHNAVIEH, ANGELA; FRAPPAOLO, ANNA; DI FRANCESCO, LAURA; PIERGENTILI, ROBERTO; SCHININA', MARIA EUGENIA
  • 11573/1672140 - 2022 - GOLPH3 protein controls organ growth by interacting with TOR signaling proteins in Drosophila (01a Articolo in rivista)
    FRAPPAOLO, ANNA; KARIMPOUR GHAHNAVIEH, ANGELA; VACCARI, THOMAS
  • 11573/1496154 - 2020 - Oncogenic roles of GOLPH3 in the physiopathology of cancer (01g Articolo di rassegna (Review))
    SECHI, STEFANO; FRAPPAOLO, ANNA; KARIMPOUR GHAHNAVIEH, ANGELA; PIERGENTILI, ROBERTO

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