The β Isoform of Human ATP-Binding Cassette B5 Transporter, ABCB5β, Localizes to the Endoplasmic Reticulum

ABCB5 beta is a member of the ABC transporter superfamily cloned from melanocytes. It has been reported as a marker of skin progenitor cells and melanoma stem cells. ABCB5 beta has also been shown to exert an oncogenic activity and promote cancer metastasis. However, this protein remains poorly characterized. To elucidate its subcellular localization, we tested several anti-ABCB5 antibodies and prepared several tagged ABCB5 beta cDNA constructs. We then used a combination of immunofluorescence and biochemical analyses to investigate the presence of ABCB5 beta in different subcellular compartments of HeLa and MelJuSo cell lines. Treatment of the cells with the proteasome inhibitor MG132 showed that part of the population of newly synthesized ABCB5 beta is degraded by the proteasome system. Interestingly, treatment with SAHA, a molecule that promotes chaperone-assisted folding, largely increased the expression of ABCB5 beta. Nevertheless, the overall protein distribution in the cells remained similar to that of control conditions; the protein extensively colocalized with the endoplasmic reticulum marker calnexin. Taken together with cell surface biotinylation studies demonstrating that the protein does not reach the plasma membrane (even after SAHA treatment), the data indicate that ABCB5 beta is a microsomal protein predominantly localized to the ER.

Automated summary

ABCB5 beta is a marker protein associated with melanoma stem cells and skin progenitor cells. The study reveals that ABCB5 beta is predominantly localized to the endoplasmic reticulum and is degraded by the proteasome system. Treatment with SAHA, a molecule promoting chaperone-assisted folding, increases the expression of ABCB5 beta.