Transducin beta-like 1X-related protein 1 (TBL1XR1)

Transducin beta-like 1X-related protein 1 (TBL1XR1) is a highly conserved member of the WD40 repeat protein family, functioning primarily as a component of nuclear receptor co-repressor (NCoR) and silencing mediator for retinoid and thyroid hormone receptor (SMRT) complexes. TBL1XR1 regulates both the repression and activation of gene transcription by facilitating large multiprotein complex assembly modulated by post-translational modifications like SUMOylation and phosphorylation. It has crucial roles in various cellular processes including cell cycle regulation, apoptosis, and cell proliferation. Its dysregulation is implicated in oncogenic signaling, cancer progression (notably in lymphomas and solid tumors), neurodevelopmental disorders, and rare syndromes. TBL1XR1 is druggable, with tegavivint representing an advanced targeting approach in preclinical and clinical cancer settings. High expression levels or genetic alterations in TBL1XR1 are linked to poor prognosis and could serve as diagnostic biomarkers in oncology.

Other names

TBL1XR1TBLR1WD40 repeat-containing protein TBL1XR1

Disruption of TBL1XR1's role in transcriptional regulation (e.g., inhibiting assembly with oncogenic signaling complexes such as Wnt/β-catenin and NF-κB pathways); Promotion of proteasomal degradation of associated proteins via the SCF/TBL1XR1 super-complex