An N-terminal region of translationally controlled tumor protein is required for its antiapoptotic activity

Abstract

Bcl-xL plays a critical role in maintaining cell survival. However, the relationship between the potential interaction of Bcl-xL with other cytosolic proteins and the regulation of cell survival remains incompletely defined. We have identified translationally controlled tumor protein (TCTP), a multifunctional protein, as a novel antiapoptotic Bcl-xL-interacting protein. TCTP interacted in vivo and in vitro with Bcl-xL, and their sites have been mapped to an N-terminal region of TCTP and the Bcl-2 homology domain 3 of Bcl-xL. Consistent with a role in maintaining T-cell survival during activation, TCTP was significantly upregulated in murine T cells activated by T-cell antigen receptor (TCR) ligation and CD28 costimulation, which was correlated with the upregulation of Bcl-xL in activated T cells. Moreover, downregulation of TCTP expression by antisense technology in T cells results in the increase of T-cell apoptosis. Furthermore, the N-terminal region of TCTP was required for its ability to inhibit apoptosis. In conclusion, this study has demonstrated that an N-terminal region of a cytosolic protein, TCTP, is required for its binding to Bcl-xL and for its antiapoptotic activity.

Roles of the translationally controlled tumour protein (TCTP) and the double-stranded RNA-dependent protein kinase, PKR, in cellular stress responses

“…Our observations on both the pattern of PKR-dependent downregulation of TCTP under Ca þ þ -stress conditions and on the cytoprotective function of TCTP 6) also suggest that the protein has broader antiapoptotic effects. Several reports support the view that TCTP undergoes direct interactions with the apoptotic machinery (Zhang et al, 2002;Liu et al, 2005;Yang et al, 2005;Susini et al, 2008) The antiapoptotic protein Bcl-xL, with which TCTP interacts, is involved in maintaining Ca þ þ homeostasis in the ER (Xu et al, 2005) and it is, therefore, possible that involvement of TCTP in the cell's response to Ca þ þ stress is based on this interaction. It was recently reported that translational downregulation of another antiapoptotic protein, Mcl-1, is an important permissive step in the apoptotic events induced by cell-stress reagents such as tunicamycin, thapsigargin and arsenite (Fritsch et al, 2007).…”

The response profiles of HSPA12A and TCTP from Mytilus galloprovincialis to pathogen and cadmium challenge

“…For MgTCTP, existence of the characteristic motif IGANASAEEAA (47aae 57aa) identified the homology of MgTCTP in the TCTP family [7]. Moreover, the typical sequence of an N-myristoylation site, GANASA (48aae53aa), in MgTCTP sequence suggested the potential anti-apoptotic activity [30].…”

Chfr interacts and colocalizes with TCTP to the mitotic spindle

“…TCTP is a ubiquitous, highly expressed protein that has been implicated in a wide variety of cellular functions, including microtubule stabilization (Gachet et al, 1999;Yarm, 2002), anti-apoptotic function, Na/KATPase inhibition (Jung et al, 2004) or as a guanine nucleotide exchange factor (Hsu et al, 2007). Furthermore, TCTP has been implicated in cancer with knockdown of TCTP, enabling tumor reversion (Tuynder et al, 2002(Tuynder et al, , 2004, whereas overexpression can protect cells from apoptosis (Liu et al, 2005;Yang et al, 2005). The specificity of the Chfr-TCTP interaction was confirmed by immunoprecipitation of endogenous Chfr from Xenopus extracts and cell lines, with a small but consistent quantity of TCTP present.…”