Abstract
ABSTRACTThe translationally controlled tumor protein (TCTP; also known as TPT1 in mammals) is highly conserved and ubiquitously expressed in eukaryotes. It is involved in growth and development, cell cycle progression, protection against cellular stresses and apoptosis, indicating the multifunctional role of the protein. Here, for the first time, we characterize the expression and function of TCTP in the human and animal pathogen, Trypanosoma brucei. We identified two paralogs (TCTP1 and TCTP2) that are differentially expressed in the life cycle of the parasite. The genes have identical 5′ untranslated regions (UTRs) and almost identical open-reading frames. The 3′UTRs differ substantially in sequence and length, and are sufficient for the exclusive expression of TCTP1 in procyclic- and TCTP2 in bloodstream-form parasites. Furthermore, we characterize which parts of the 3′UTR are needed for TCTP2 mRNA stability. RNAi experiments demonstrate that TCTP1 and TCTP2 expression is essential for normal cell growth in procyclic- and bloodstream-form parasites, respectively. Depletion of TCTP1 in the procyclic form cells leads to aberrant cell and mitochondrial organelle morphology, as well as enlarged, and a reduced number of, acidocalcisomes.
Highlights
Since the time of its discovery ∼30 years ago (Chitpatima et al, 1988), translationally controlled tumor protein (TCTP) has continuously attracted research interest due to the high conservation among eukaryotes and involvement in a large number of biological processes (Bommer and Thiele, 2004)
TCTP paralogs expression in different life cycle stages of T. brucei When we probed for TCTP mRNA expression in BSF and procyclic forms (PCFs) parasites, we found that two different isoforms of the gene were expressed (Fig. 2A)
More than 300 publications describe the large variety of processes TCTP might be involved in, including apoptosis, cell cycle regulation, stress response, just to name a few
Summary
Since the time of its discovery ∼30 years ago (Chitpatima et al, 1988), TCTP ( known as TPT1 in mammals) has continuously attracted research interest due to the high conservation among eukaryotes and involvement in a large number of biological processes (Bommer and Thiele, 2004). Different studies have shown that TCTP is involved in many biological processes depending on the type of the cells/tissue, most notably growth and development, apoptosis, protection against cellular stresses and the cell cycle (Berkowitz et al, 2008; Cao et al, 2010; Chan et al, 2012b; Chen et al, 2007; Gnanasekar et al, 2009; Gnanasekar and Ramaswamy, 2007; Hsu et al, 2007; Mak et al, 2001). The protein is primarily localized in the cytosol; in mammals and yeast it has been shown that TCTP can localize to the nucleus or mitochondria, respectively, when cells are exposed to certain stress conditions (Diraison et al, 2011; Rid et al, 2010; Rinnerthaler et al, 2006)
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