AIRC IG2017. Golgi phosphoprotein 3 and membrane trafficking in cytokinesis and cell proliferation (DSB.AD005.053)

Thematic area

Biomedical sciences

Project area

Structure responsible for the research project

Institute of molecular biology and pathology (IBPM)

Project manager

MARIAGRAZIA GIANSANTI
Phone number: 0649912716
Email: mariagrazia.giansanti@uniroma1.it

Abstract

Golgi phosphoprotein 3 (GOLPH3) has been characterized as a Phosphatidylinositol 4-Phosphate [PI(4)P] effector at the Golgi, required for vesicle trafficking and Golgi glycosylation. Encoded by a gene on chromosome 5p13, GOLPH3 is frequently amplified in several solid tumor types including breast cancer, melanoma and lung cancer. Moreover GOLPH3 overexpression is correlated with poor prognosis in multiple cancer types. It has been suggested that upregulation of GOLPH3 may promote tumorigenesis by enhancing activity of the mammalian target of rapamycin (mTOR). However the molecular pathways through which GOLPH3 acts in malignant transformation require further investigation.
We demonstrated that GOLPH3 controls cytokinesis by associating with proteins of both the vesicle trafficking and cytokinesis machineries. Moreover our preliminary data suggest that GOLPH3 might interact with components of the TOR signaling pathway. We believe that dissecting the signaling pathways that involve GOLPH3 in cytokinesis and cell proliferation, will clarify the molecular mechanisms underlying its oncogenic activity.

Goals

One immediate aim of our new research project will be to investigate the molecular mechanisms underlying GOLPH3 function in cytokinesis and GOLPH3 cell cycle-dependent phosphorylation changes. This will be highly relevant to cancer biology because cytokinesis failures lead to tetraploidy, which promotes tumorigenesis and chromosome instability, accelerates cancer genome evolution and has been correlated with poor prognosis. To gain further insight into GOLPH3 function in vesicle trafficking, we will analyze the molecular interactions of GOLPH3 with regulators of endocytic/secretory pathways. Because the oncogenic activity of GOLPH3 might be linked to altered Golgi glycosylation we will use Drosophila to analyze the GOLPH3-dependent glycosylation effects in the whole organism by applying multi-dimensional ion trap mass spectrometry. Finally we will use the sophisticated genetic tools offered by the Drosophila model system to explore the relationship of GOLPH3 with the TOR signaling and how this may influence cell growth and proliferation.

Start date of activity

01/01/2018

Keywords

GOLPH3, CITOCHINESI, DIVISIONE CELLULARE

Last update: 22/04/2025