Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2023

An isoform specific role of autophagy protein ATG7 in cancer

Höfundar / Authors: Clémence Larat (1), Margrét Hela Ögmundsdóttir (1)

Starfsvettvangur / Affiliations: 1. Biochemistry department HÍ

Kynnir / Presenter: Clémence Larat

Autophagy has been shown to be involved in cancer initiation and development, either in a tumor-suppressive or promotive manner. The autophagy protein ATG7 has been linked with numerous pathologies and cancers, including Pancreatic Ductal Adenocarcinoma (PDAC). We previously identified two isoforms of ATG7 and showed that, unlike the long isoform ATG7(1), the short isoform ATG7(2) does not have the characterized activity of the protein. ATG7 has also been shown to regulate the activity and degradation of YAP. YAP has been shown to be a key modulator of metastasis and tumor immunity, and is linked with bad prognosis in PDAC. Our expression analysis data shows an up-regulation of ATG7(2) expression in cancer, as well as a correlation of high ATG7(2) expression with bad prognosis in PDAC. Additionally, we analyzed the interactome of both isoforms and observed that, unlike ATG7(1), ATG7(2) interacts with proteins involved in non-autophagic pathways. One of these proteins is AJUBA, which has both cytoplasmic and nuclear activities. In the cytoplasm, it regulates many pathways, including JAK-STAT, ERK and the Hippo pathway, which regulates the activity and degradation of YAP/TAZ. In the nucleus, AJUBA regulates the activity of many transcription factors, subsequently regulating the expression of a broad number of genes. Here we focus on the interaction between ATG7(2) and AJUBA, and its downstream effect on YAP/TAZ phosphorylation, tumorigenesis, metastasis and immune infiltration