Characterization of the Translationally Controlled Tumor Protein (TCTP) Interactome Reveals Novel Binding Partners in Human Cancer Cells

Translationally
controlled tumor protein (TCTP) is a highly conserved
housekeeping protein present in eukaryotic organisms. It is involved
in regulating many fundamental processes and plays a critical role
in tumor reversion and tumorigenesis. Increasing evidence suggests
that TCTP plays a role in the regulation of cell fate determination
and is a promising therapeutic target for cancer. To decipher the
exact mechanisms by which TCTP functions and how all these functions
are integrated, we analyzed the interactome of TCTP in HeLa cells
by coimmuno­precipitation (IP) and mass spectrometry (MS). A
total of 98 proteins were identified. We confirmed the in vitro and
in vivo association of TCTP with six of the identified binding proteins
using reciprocal IP and bimolecular fluorescence complementation (BiFC)
analysis, respectively. Moreover, TCTP interacted with Y-box-binding
protein 1 (YBX1), and their interaction was localized to the N-terminal
region of TCTP and the 1–129 amino acid (aa) residues of YBX1.
The YBX1 protein plays an important role in cell proliferation, RNA
splicing, DNA repair, drug resistance, and stress response to extracellular
signals. These data suggest that the interaction of TCTP with YBX1
might cooperate or coordinate their functions in the control of diverse
regulatory pathways in cancer cells. Taken together, our results not
only reveal a large number of TCTP-associated proteins that possess
pleiotropic functions, but also provide novel insights into the molecular
mechanisms of TCTP in tumorigenesis.