Complex relationship between TCTP, microtubules and actin microfilaments regulates cell shape in normal and cancer cells

Translationally controlled tumor-associated protein (TCTP) is a ubiquitous and highly conserved protein implicated in cancers. Here, we demonstrate that interactions of TCTP with microtubules (MTs) are functionally important but indirect, and we reveal novel interaction of TCTP with the actin cytoskeleton. Firstly, immunofluorescence in Xenopus XL2 cells revealed cytoplasmic fibers stained with TCTP but not with tubulin antibodies, as well as MTs free of TCTP. Furthermore, TCTP localized to a subset of actin-rich fibers in migrating cells. Secondly, Xenopus laevis TCTP did not affect in vitro assembly/disassembly of MTs and lacked MT-binding affinity both in pull-down assays and in cell-free extracts. Although TCTP also failed to bind to purified filamentous actin (F-actin), it was associated with microfilaments in cell-free extracts. Thirdly, TCTP concentrated in mitotic spindle did not colocalize with MTs and was easily dissociated from these structures except at the poles. Finally, RNA interference knockdown of TCTP in XL2 and HeLa cells provoked drastic, MT-dependent shape change. These data show that although TCTP interacts with MTs, it does not behave as classic MT-associated protein. Our evidence for an association of TCTP with F-actin structures, and for an involvement in cell shape regulation, implicates this protein in integrating cytoskeletal interactions both in interphase and mitosis providing a new avenue to fully understand the role of TCTP.