TY - JOUR
T1 - Identification of two novel heterodimeric ABC transporters in melanoma
T2 - ABCB5β/B6 and ABCB5β/B9
AU - Gerard, Louise
AU - Duvivier, Laurent
AU - Fourrez, Marie
AU - Salazar, Paula
AU - Sprimont, Lindsay
AU - Xia, Di
AU - Ambudkar, Suresh V.
AU - Gottesman, Michael M.
AU - Gillet, Jean Pierre
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2024/2
Y1 - 2024/2
N2 - ABCB5 is a member of the ABC transporter superfamily composed of 48 transporters, which have been extensively studied for their role in cancer multidrug resistance and, more recently, in tumorigenesis. ABCB5 has been identified as a marker of skin progenitor cells, melanoma, and limbal stem cells. It has also been associated with multidrug resistance in several cancers. The unique feature of ABCB5 is that it exists as both a full transporter (ABCB5FL) and a half transporter (ABCB5β). Several studies have shown that the ABCB5β homodimer does not confer multidrug resistance, in contrast to ABCB5FL. In this study, using three complementary techniques, (1) nanoluciferase-based bioluminescence resonance energy transfer, (2) coimmunoprecipitation, and (3) proximity ligation assay, we identified two novel heterodimers in melanoma: ABCB5β/B6 and ABCB5β/B9. Both heterodimers could be expressed in High-Five insect cells and ATPase assays revealed that both functional nucleotide-binding domains of homodimers and heterodimers are required for their basal ATPase activity. These results are an important step toward elucidating the functional role of ABCB5β in melanocytes and melanoma.
AB - ABCB5 is a member of the ABC transporter superfamily composed of 48 transporters, which have been extensively studied for their role in cancer multidrug resistance and, more recently, in tumorigenesis. ABCB5 has been identified as a marker of skin progenitor cells, melanoma, and limbal stem cells. It has also been associated with multidrug resistance in several cancers. The unique feature of ABCB5 is that it exists as both a full transporter (ABCB5FL) and a half transporter (ABCB5β). Several studies have shown that the ABCB5β homodimer does not confer multidrug resistance, in contrast to ABCB5FL. In this study, using three complementary techniques, (1) nanoluciferase-based bioluminescence resonance energy transfer, (2) coimmunoprecipitation, and (3) proximity ligation assay, we identified two novel heterodimers in melanoma: ABCB5β/B6 and ABCB5β/B9. Both heterodimers could be expressed in High-Five insect cells and ATPase assays revealed that both functional nucleotide-binding domains of homodimers and heterodimers are required for their basal ATPase activity. These results are an important step toward elucidating the functional role of ABCB5β in melanocytes and melanoma.
KW - ABC transporter
KW - chemoresistance
KW - heterodimerization
KW - melanoma
KW - nanoluciferase-based bioluminescence resonance energy transfer (NanoBRET)
KW - protein–protein interaction
KW - proximity ligation assay (PLA)
UR - http://www.scopus.com/inward/record.url?scp=85182388456&partnerID=8YFLogxK
U2 - 10.1016/j.jbc.2023.105594
DO - 10.1016/j.jbc.2023.105594
M3 - Article
C2 - 38145744
AN - SCOPUS:85182388456
SN - 0021-9258
VL - 300
JO - The Journal of Biological Chemistry
JF - The Journal of Biological Chemistry
IS - 2
M1 - 105594
ER -
