title: Phosphorylation of threonine 190 is essential for nuclear localization and endocytosis of the FTS (Fused Toes Homolog) protein.
abstract: Fused Toes Homolog (FTS) is a member of a group of proteins termed as E2 variants and this group of proteins lacks an active cysteine residue that is required for ubiquitin transfer. We have identified the expression of this protein in early neoplastic stages of cervical cancer and its translocation into nucleus from cytoplasm upon irradiation. Here we have reported that a threonine residue at position 190 is essential for its nucleocytoplasmic shuttling and function. Upon LMB treatment we found that FTS was located in the nucleus and it suggests that direct role of nuclear export signal (NES) is required for the binding to CRM1 and facilitates nuclear export. The threonine residue was phosphorylated and promoted the phosphorylation of EGFR, p38 and JNK facilitating vesicular trafficking of early to late endosomes. Mutational change of the threonine into alanine resulted in the cytoplasmic localization of FTS and failed to phosphorylate EGFR and its downstream effector proteins. In addition the mutation also reduced the number of early endosomes formed and also resulted in the clustering of late endosomes around the perinuclear region. These data suggest that threonine residue of FTS at position 190 is not only essential for its function but also for the formation, maturation and trafficking of early endosomes to late endosome/lysosome, as well as we speculate that FTS may function at a connection point in the vesicle tethering.
authors.affiliation: Department of Radiation Oncology, Chungbuk National University College of Medicine, Cheongju, Republic of Korea.
authors.forename: Arunkumar
authors.initials: A
authors.lastname: Anandharaj
authors.forename: Jae-Ran
authors.initials: JR
authors.lastname: Yu
authors.forename: Woo-Yoon
authors.initials: WY
authors.lastname: Park
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D049790:Nuclear Export Signals; D010766:Phosphorylation / Q000187:drug effects; D010769:Phosphothreonine / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005231:Fatty Acids, Unsaturated; D049790:Nuclear Export Signals; D010769:Phosphothreonine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; C038753:leptomycin B