T-complex protein 1 subunit alpha (TCP1) (TCP1)

T-complex protein 1 (TCP1), also known as CCT-alpha, is a core subunit of the chaperonin-containing T-complex (CCT), also known as the TRiC complex [1, 4, 11]. This cytosolic molecular chaperone is essential for the ATP-dependent folding of approximately 10% of the eukaryotic proteome, including critical cytoskeletal proteins such as actin and tubulin [1, 5, 11]. TCP1 is frequently upregulated in various malignancies, including acute myeloid leukemia, small cell lung cancer, and breast cancer, where it facilitates the folding and stability of oncogenic proteins like STAT3, MYC, and KRAS [6, 12, 16]. Due to its central role in maintaining cellular proteostasis and supporting the cancer phenotype, TCP1 is considered a promising therapeutic target [6, 12, 13]. Inhibition of TCP1 or the TRiC complex leads to the accumulation of misfolded proteins, proteostatic stress, and eventual cell death in cancer cells [2, 12]. Experimental inhibitors, such as the peptide CT20p and the small molecule fingolimod, have shown efficacy in disrupting TCP1 function in preclinical models [6, 12, 14]. However, the essential nature of its housekeeping functions in normal cells presents a significant challenge for developing therapies with a wide therapeutic window [12].

Other names

CCT-alphaCCT1CCTaTCP-1-alphaChaperonin containing T-complex polypeptide 1 subunit 1D6S230ETCP-1

Chaperonin inhibition, Inhibition of protein folding, Disruption of TRiC/CCT complex assembly