The translationally controlled tumour protein (TCTP)

Abstract

The translationally controlled tumour protein (TCTP) is a highly conserved protein that is widely expressed in all eukaryotic organisms. Based on its sequence, TCTP was listed as a separate protein family in protein databases but the recent elucidation of the solution structure of the fission yeast orthologue places it close to a family of small chaperone proteins. The molecular functions determined so far, Ca²⁺- and microtubule-binding, have been mapped to an α-helical region of the molecule. TCTP expression is highly regulated both at the transcriptional and translational level and by a wide range of extracellular signals. TCTP has been implicated in important cellular processes, such as cell growth, cell cycle progression, malignant transformation and in the protection of cells against various stress conditions and apoptosis. In addition, an extracellular, cytokine-like function has been established for TCTP, and the protein has been implicated in various medically relevant processes.

Introduction

The translationally controlled tumour protein (TCTP) was discovered about 20 years ago by three groups interested in translationally regulated genes. They named this protein P21, Q23 and P23, respectively (reviewed in Gachet et al. (1999)). The cDNA sequences of the mouse (Chitpatima, Makrides, Bandyopadhyay, & Brawerman, 1988) and the human protein (Gross, Gaestel, Boehm, & Bielka, 1989) were published in the late eighties. At this time the name ‘translationally controlled tumour protein’ was coined (Gross et al., 1989), based on the fact that the cDNA was cloned from a human tumour and on the observation that TCTP is regulated at the translational level. Elucidation of the primary sequence did not reveal any similarity with other protein families. Only the recent determination of the solution structure of the fission yeast protein (Thaw et al., 2001) indicated similarity with a small chaperone family.

Recently TCTP has attracted the attention of an increasing number of researchers interested in various biologically and medically relevant processes. This is largely due to the fact that TCTP levels are highly regulated in response to a wide range of extracellular stimuli. A series of recent reports highlighted the importance of TCTP for cell cycle progression and malignant transformation. In addition, TCTP was shown to display an extracellular function as a histamine release factor and to have anti-apoptotic activity. These findings led the authors to suggest yet other names for this protein, such as ‘histamine releasing factor (HRF)’ (MacDonald, Rafnar, Langdon, & Lichtenstein, 1995) and ‘fortilin’ (Li, Zhang, & Fujise, 2001). However, each of these designations emphasises only a particular function of this interesting protein and does not fully appreciate its wide-ranging biological importance.