Ad-ATRA-2

Amino Acid Sequence

3D Structure (/structures/AF-P29373-F1-model_v6.cif)

Function

Transports retinoic acid to the nucleus. Regulates the access of retinoic acid to the nuclear retinoic acid receptors.

Mechanism

The ubiquitin-proteasome pathway (UPP) constitutes the principal pathway for protein degradation in eukaryotic cells, mediating the breakdown of target proteins through ubiquitin tagging and subsequent proteasomal degradation. In an ATP-dependent manner, the ubiquitin-activating enzyme (E1) activates ubiquitin (Ub) and conjugates it to a ubiquitin-conjugating enzyme (E2). E3 ligase subsequently catalyzes the transfer of Ub to the target protein, leading to the formation of a polyubiquitin chain that completes the ubiquitination mark. The 19S regulatory particle of the 26S proteasome recognizes this ubiquitination signal and, after deubiquitination, mediates the ATP-dependent delivery of the substrate into the 20S proteasome for degradation.

Description

We also examined the involvement of the proteasome in HyT-mediated degradation. The 2 and 3-induced reductions of CRABP-2 were completely inhibited in the presence of the proteasome inhibitor MG132, suggesting that 2 and 3 induce the proteasomal degradation of CRABP-2 (Figure 4). This result clearly indicated the involvement of proteasome activity for the reduction of the target protein.

Description

We examined the protein reduction activity of 2, 3, and 4 using various cell lines. In MCF-7 cells; 2 and 3 effectively reduced the CRABP-2 protein level, whereas 4, which contained the less hydrophobic benzyl moiety, showed attenuated protein knockdown activity (Figure 3A and Figure S5). The CRABP2 reduction activity of 3 was similar to that of 1 in MCF7 cells (Figure S6).