TCID (Synonyms: UCH-L3 Inhibitor)

TCID is a potent, selective and cell-permeable inhibitor of UCHL3 (ubiquitin carboxyl-terminal esterase L3 (ubiquitin thiolesterase)) with IC50 of 0.6 μm. It is also a 125 fold less potent inhibitor of UCH-L1 (IC50 = 75 μm). [1]

UCHL3 belongs to the deubiquitinating enzyme family that removes ubiquitin from polypeptides. It processes ubiquitin precursors and ubiquitinated proteins to regulate cellular ubiquitin levels.

GlyT2 ubiquitination was diminished by inhibition of UCHL3 with TCID (10 μm) and inhibition of UCHL1 with LDN-57444 (10 μm) in brainstem and spinal cord primary neurons, and the effect was more significant when cell was treated with the inhibitors for a prolonged period. [2] In transfected MDCK cells, TCID (10 μm for 30 mins) was not able to affect the UCH-L1 inhibitor promoted accumulation of YFP-GLT-1 in intracellular vesicles. [3]

References:
[1] Liu Y, Lashuel HA, Choi S, Xing X, Case A, Ni J, Yeh LA, Cuny GD, Stein RL, Lansbury PT Jr.  Discovery of inhibitors that elucidate the role of UCH-L1 activity in the H1299 lung cancer cell line.  Chem Biol. 2003 Sep;10(9):837-46.
[2] de Juan-Sanz J, Núñez E, López-Corcuera B, Aragón C.  Constitutive endocytosis and turnover of the neuronal glycine transporter GlyT2 is dependent on ubiquitination of a C-terminal lysine cluster.  PLoS One. 2013;8(3):e58863.
[3] Martínez-Villarreal J, García Tardón N, Ibáñez I, Giménez C, Zafra F.  Cell surface turnover of the glutamate transporter GLT-1 is mediated by ubiquitination/deubiquitination.  Glia. 2012 Sep;60(9):1356-65.