Targeted Degradation of ABC Transporters in Health and Disease

Overview

Journal J Bioenerg Biomembr

Publisher Springer

Specialties Biochemistry
Biology
Endocrinology

Date 2007 Nov 1

PMID 17972020

Citations 6

Authors

Daphne Nikles

Robert Tampe

Affiliations

Soon will be listed here.

Abstract

ATP binding cassette (ABC) transporters comprise an extended protein family involved in the transport of a broad spectrum of solutes across membranes. They consist of a common architecture including two ATP-binding domains converting chemical energy into conformational changes and two transmembrane domains facilitating transport via alternating access. This review focuses on the biogenesis, and more precisely, on the degradation of mammalian ABC transporters in the endoplasmic reticulum (ER). We enlighten the ER-associated degradation pathway in the context of misfolded, misassembled or tightly regulated ABC transporters with a closer view on the cystic fibrosis transmembrane conductance regulator (CFTR) and the transporter associated with antigen processing (TAP), which plays an essential role in the adaptive immunity. Three rather different scenarios affecting the stability and degradation of ABC transporters are discussed: (1) misfolded domains caused by a lack of proper intra- and intermolecular contacts within the ABC transporters, (2) deficient assembly with auxiliary factors, and (3) arrest and accumulation of an intermediate or 'dead-end' state in the transport cycle, which is prone to be recognized by the ER-associated degradation machinery.

Citing Articles

Cellular Processing of the ABCG2 Transporter-Potential Effects on Gout and Drug Metabolism.

Mozner O, Bartos Z, Zambo B, Homolya L, Hegedus T, Sarkadi B Cells. 2019; 8(10).

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Development of CFTR Structure.

Patrick A, Thomas P Front Pharmacol. 2012; 3:162.

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Mutation of Glu521 or Glu535 in cytoplasmic loop 5 causes differential misfolding in multiple domains of multidrug and organic anion transporter MRP1 (ABCC1).

Iram S, Cole S J Biol Chem. 2012; 287(10):7543-55.

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Posttranslational negative regulation of glycosylated and non-glycosylated BCRP expression by Derlin-1.

Sugiyama T, Shuto T, Suzuki S, Sato T, Koga T, Suico M Biochem Biophys Res Commun. 2010; 404(3):853-8.

PMID: 21184741 PMC: 4457448. DOI: 10.1016/j.bbrc.2010.12.074.

Location of the beta 4 transmembrane helices in the BK potassium channel.

Wu R, Chudasama N, Zakharov S, Doshi D, Motoike H, Liu G J Neurosci. 2009; 29(26):8321-8.

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References

Carvalho P, Goder V, Rapoport T . Distinct ubiquitin-ligase complexes define convergent pathways for the degradation of ER proteins. Cell. 2006; 126(2):361-73. DOI: 10.1016/j.cell.2006.05.043. View

Wiertz E, Hill A, Tortorella D, Ploegh H . Cytomegaloviruses use multiple mechanisms to elude the host immune response. Immunol Lett. 1997; 57(1-3):213-6. DOI: 10.1016/s0165-2478(97)00073-4. View

Carlson E, Pitonzo D, Skach W . p97 functions as an auxiliary factor to facilitate TM domain extraction during CFTR ER-associated degradation. EMBO J. 2006; 25(19):4557-66. PMC: 1589997. DOI: 10.1038/sj.emboj.7601307. View

Ahner A, Nakatsukasa K, Zhang H, Frizzell R, Brodsky J . Small heat-shock proteins select deltaF508-CFTR for endoplasmic reticulum-associated degradation. Mol Biol Cell. 2006; 18(3):806-14. PMC: 1805084. DOI: 10.1091/mbc.e06-05-0458. View

Papadopoulos M, Momburg F . Multiple residues in the transmembrane helix and connecting peptide of mouse tapasin stabilize the transporter associated with the antigen-processing TAP2 subunit. J Biol Chem. 2007; 282(13):9401-9410. DOI: 10.1074/jbc.M610429200. View

Knop M, Finger A, Braun T, Hellmuth K, Wolf D . Der1, a novel protein specifically required for endoplasmic reticulum degradation in yeast. EMBO J. 1996; 15(4):753-63. PMC: 450274. View

Pety de Thozee C, Cronin S, Goj A, Golin J, Ghislain M . Subcellular trafficking of the yeast plasma membrane ABC transporter, Pdr5, is impaired by a mutation in the N-terminal nucleotide-binding fold. Mol Microbiol. 2007; 63(3):811-25. DOI: 10.1111/j.1365-2958.2006.05562.x. View

Buschhorn B, Kostova Z, Medicherla B, Wolf D . A genome-wide screen identifies Yos9p as essential for ER-associated degradation of glycoproteins. FEBS Lett. 2004; 577(3):422-6. DOI: 10.1016/j.febslet.2004.10.039. View

Neumann L, Abele R, Tampe R . Thermodynamics of peptide binding to the transporter associated with antigen processing (TAP). J Mol Biol. 2002; 324(5):965-73. DOI: 10.1016/s0022-2836(02)01148-8. View

10.

Schmitt L, Tampe R . Structure and mechanism of ABC transporters. Curr Opin Struct Biol. 2002; 12(6):754-60. DOI: 10.1016/s0959-440x(02)00399-8. View

11.

Lindquist J, Jensen O, Mann M, Hammerling G . ER-60, a chaperone with thiol-dependent reductase activity involved in MHC class I assembly. EMBO J. 1998; 17(8):2186-95. PMC: 1170563. DOI: 10.1093/emboj/17.8.2186. View

12.

McCracken A, Brodsky J . Recognition and delivery of ERAD substrates to the proteasome and alternative paths for cell survival. Curr Top Microbiol Immunol. 2006; 300:17-40. DOI: 10.1007/3-540-28007-3_2. View

13.

Conseil G, Deeley R, Cole S . Functional importance of three basic residues clustered at the cytosolic interface of transmembrane helix 15 in the multidrug and organic anion transporter MRP1 (ABCC1). J Biol Chem. 2005; 281(1):43-50. DOI: 10.1074/jbc.M510143200. View

14.

Ye Y, Meyer H, Rapoport T . The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol. Nature. 2001; 414(6864):652-6. DOI: 10.1038/414652a. View

15.

Cruciat C, Hassler C, Niehrs C . The MRH protein Erlectin is a member of the endoplasmic reticulum synexpression group and functions in N-glycan recognition. J Biol Chem. 2006; 281(18):12986-93. DOI: 10.1074/jbc.M511872200. View

16.

Garbi N, Tiwari N, Momburg F, Hammerling G . A major role for tapasin as a stabilizer of the TAP peptide transporter and consequences for MHC class I expression. Eur J Immunol. 2003; 33(1):264-73. DOI: 10.1002/immu.200390029. View

17.

Dean M, Rzhetsky A, Allikmets R . The human ATP-binding cassette (ABC) transporter superfamily. Genome Res. 2001; 11(7):1156-66. DOI: 10.1101/gr.184901. View

18.

Janas E, Hofacker M, Chen M, Gompf S, van der Does C, Tampe R . The ATP hydrolysis cycle of the nucleotide-binding domain of the mitochondrial ATP-binding cassette transporter Mdl1p. J Biol Chem. 2003; 278(29):26862-9. DOI: 10.1074/jbc.M301227200. View

19.

Heemels M, Schumacher T, Wonigeit K, Ploegh H . Peptide translocation by variants of the transporter associated with antigen processing. Science. 1993; 262(5142):2059-63. DOI: 10.1126/science.8266106. View

20.

Meusser B, Hirsch C, Jarosch E, Sommer T . ERAD: the long road to destruction. Nat Cell Biol. 2005; 7(8):766-72. DOI: 10.1038/ncb0805-766. View