AIRC: IG 2020 ID 24942 - Exploring the role of Alpha-tubulin N-acetyltransferase 1 in cancer: from molecular mechanisms to therapeutic targets (DSB.AD006.313)

Thematic area

Biomedical sciences

Project area

Structure responsible for the research project

Institute of molecular biology and pathology (IBPM)

Project manager

DANIELA TRISCIUOGLIO
Phone number: 06 49917515
Email: daniela.trisciuoglio@uniroma1.it

Abstract

The cytoskeleton is a complex and dynamic network of microtubules and actin filaments with a role in cell morphogenesis, intracellular transport and cell motility. Among post-translational modifications regulating the cytoskeleton, tubulin acetylation at lysine-40 is known to control diverse cellular functions often deregulated in cancer, as microtubule dynamics, cell migration and autophagy. While the role of tubulin deacetylating enzymes is well studied in cancer, the role of alpha-tubulin N-acetyltransferase 1 (ATAT-1), the main tubulin-acetylating enzyme, remains underexplored yet. Here, we put forth the hypothesis that ATAT-1 exerts a pro-oncogenic role in lung cancer, and that accordingly lung cancer patients could benefit from pharmacological inhibition of ATAT-1 activity.
The expected results will be important to i) expand our understanding of how ATAT-1 functions, ii) define the mechanisms of ATAT-1 in microtubules-actin cross-regulation and iii) identify new ATAT-1 substrates and pathways. It will thereby provide a deeper understanding of the molecular activities and interactions that underlie processes such as cell migration, cell division, and autophagy.

Goals

1)To study in vitro the effect of ATAT-1 on cytoskeleton rearrangements and cancer aggressiveness;
2) To identify novel targets and pathways regulated by ATAT-1;
3) To identify new small molecules inhibiting ATAT-1;
4) To validate of the prognostic role of ATAT-1 in lung cancer.

Start date of activity

01/01/2021

Keywords

Protein acetylation, Cytoskeleton, Lung cancer

Last update: 19/04/2024