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.
Original language | English (US) |
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Pages (from-to) | 721-728 |
Number of pages | 8 |
Journal | International Journal of Biological Macromolecules |
Volume | 49 |
Issue number | 4 |
DOIs | |
State | Published - Nov 1 2011 |
Externally published | Yes |
Bibliographical note
Funding Information:The authors would like to thank Mrs. Jeong-Seon Jeon for her excellent technical assistance. This research was supported by the program of Basic Atomic Energy Research Institute (BAERI), which is a part of the Nuclear R&D Programs funded by the Ministry of Education, Science and Technology (MEST) of Korea in 2010.
Keywords
- E2 variant
- EGFR
- Endosomes
- FTS
- Nuclear export signal
- Phosphorylation