Líffræðifélag Íslands
Líffræðiráðstefnan 2015
Erindi/veggspjald / Talk/poster V80
Ásgeir Örn Arnþórsson, Ingibjörg Sigvaldadóttir, Katrín Möller, Sara Sigurbjörnsdóttir, Margrét H. Ögmundsdóttir and Eiríkur Steingrímsson
Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik, Iceland
Kynnir / Presenter: Ásgeir Örn Arnþórsson
Tengiliður / Corresponding author: Ásgeir Örn Arnþórsson (aoa12@hi.is)
Autophagy and lysosomal activity have been highlighted as being important for melanoma growth. TFEB and TFE3, members of the MiT/TFE family of transcription factors, are regulators of lysosomes/autophagy through mTORC1 activity and nutrient sensing. When nutrients are plentiful TFEB and mTORC1 are redistributed to lysosomes where mTORC1 phosphorylates TFEB, preventing it from entering the nucleus and activating lysosomal genes. MITF, a member of the same family, is a master regulator of melanocytes, regulating most processes in this cell type. MITF has furthermore been termed a lineage specific oncogene in melanoma. MITF has recently been suggested to also play a role in lysosomal activity. A melanocyte specific isoform of MITF (MITF-M) resides within the nucleus of melanoma cells as it is missing the mTORC1 interaction site that keeps TFEB and TFE3 cytoplasmic. Our aim is to identify which isoforms of TFEB and TFE3 are present in melanoma cells. We performed 5’RACE on mRNA from 501mel melanoma cells. Our results show that in addition to a full length isoform, these cells also express a shorter TFEB isoform, similar to MITF-M. We are currently analyzing TFE3 to determine if other isoforms are present. All family members bind to the same DNA elements and can homo- and heterodimerize, which raises the question of how different roles are determined. The property and location of these isoforms will improve our understanding of the interplay between the MITF/TFE family members and their individual roles in lysosomal control in melanomas.