Translationally controlled tumor protein (TCTP) – p53 regulatory complex (TCTP-p53 complex)

The Translationally controlled tumor protein (TCTP) – p53 regulatory complex is a critical protein-protein interaction that governs the stability and tumor-suppressive activity of the p53 protein. TCTP, also known as Fortilin or TPT1, directly interacts with p53 to promote its ubiquitination and subsequent degradation via the MDM2 pathway, thereby inhibiting p53-mediated apoptosis and cell cycle arrest (Amson et al., 2012, Nature Medicine; Rho et al., 2011, FEBS Letters). This regulatory loop is often hijacked in various cancers, where TCTP overexpression leads to the functional inactivation of wild-type p53, contributing to tumor progression and resistance to therapy (Tuynder et al., 2004, PNAS). Therapeutic targeting of this complex aims to disrupt the TCTP-p53 interaction to restore p53 levels and its downstream apoptotic signaling. Small molecules such as Dihydroartemisinin (DHA) and certain repurposed drugs like Sertraline and Thioridazine have been identified to bind TCTP, effectively reducing its concentration or blocking its interaction with p53 (Amson et al., 2012). This approach is particularly promising for treating malignancies that retain wild-type p53 but exhibit high TCTP expression, offering a strategy to reactivate endogenous tumor suppression (UniProt P13693).

Other names

TCTP-p53 interactionFortilin-p53 complexTPT1-p53 complexTranslationally-controlled tumor protein-p53 complex

Inhibition of the TCTP-p53 protein-protein interaction, leading to the stabilization of p53 and induction of p53-dependent apoptosis (Amson et al., 2012).