The uniqueness of ABCB5 as a full transporter ABCB5FL and a half-transporter-like ABCB5β

Abstract

The ABCB5 gene encodes several isoforms, including two transporters (i.e., ABCB5FL, ABCB5β) and several soluble proteins, such as ABCB5α which has been hypothesized to have a regulatory function. ABCB5FL is a full ABC transporter and is expressed in the testis and prostate, whereas ABCB5β is an atypical half-transporter with a ubiquitous expression pattern. ABCB5β has been shown to mark cancer stem cells in several cancer types. In addition, ABCB5β and ABCB5FL have been shown to play a role in tumorigenesis and multidrug resistance. However, ABCB5β shares its entire protein sequence with ABCB5FL, making them difficult to distinguish. It cannot be excluded that some biological effects described for one transporter may be mediated by the other isoform. Therefore, it is difficult to interpret the available data and some controversies remain regarding their function in cancer cells. In this review, we discuss the data collected on ABCB5 isoforms over the last 20 years and propose a common ground on which we can build further to unravel the pathophysiological roles of ABCB5 transporters.

Keywords: ABC transporter; cancer stem cells; half-transporter; multidrug resistance.

Figure 1

Topology of ABCB5FL and ABCB5β. Two-dimensional representation of the topology of ABCB5FL and ABCB5β based on CCTOP prediction^[9]. ABCB5FL is composed of 12 TMH (shown in blue) and two NBD (shown in orange). The NBDs are composed of an A-Loop, Walker A, Q-Loop, signature motif, Walker B, D-Loop, and H-Loop; the amino acid sequences are detailed in the corresponding boxes. ABCB5β consists of 6 TMHs and two NBDs. The N-terminal NBD lacks the A-Loop and the Walker A motif. CCTOP: Consensus Constrained TOPology prediction; TMH: transmembrane helice; NBD: nucleotide-binding domain.

Figure 2

Tissue and intracellular localization of ABCB5FL and ABCB5β. (A) Representation of human ABCB5 tissue localization based on ABCB5FL and ABCB5β mRNA detection from^[1,6,18]. Light blue represents ABCB5β localization. Dark blue represents ABCB5FL localization; (B) Schematic representation of the proposed intracellular localization of ABCB5β in light blue^[2,19,20] and one of the two longest isoforms in gray^[21]. Results obtained using antibodies, for which more validation is necessary, are highlighted by a pink antibody. Results obtained with tagged protein are highlighted by a green round schematizing a GFP tag. PM: Plasma membrane; ER: endoplasmic reticulum; PL: phagolysosomes; GFP: green fluorescent protein.