Itch/AIP4 Mediates Deltex Degradation Through the Formation of K29-linked Polyubiquitin Chains

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2006 Oct 10

PMID 17028573

Citations 106

Authors

Patricia Chastagner

Alain Israel

Christel Brou

Affiliations

Soon will be listed here.

Abstract

Deltex (DTX) and AIP4 are the human orthologues of the Drosophila deltex and Suppressor of deltex, which have been genetically described as being antagonistically involved in the Notch signalling pathway. Both genes encode E3 ubiquitin ligases of the RING (Really interesting new gene)-H2 and HECT (Homologous to E6AP carboxyl terminus) families, respectively. In an attempt to understand the molecular basis of their genetic interactions, we studied the relationship between DTX and AIP4 in the absence of activation of the Notch pathway. We show here that both molecules interact and partially colocalize to endocytic vesicles, and that AIP4 targets DTX for lysosomal degradation. Furthermore, AIP4-generated polyubiquitin chains are mainly conjugated through lysine 29 of ubiquitin in vivo, indicating a link between this type of chain and lysosomal degradation.

Citing Articles

The Ubiquitin Tale: Current Strategies and Future Challenges.

Upadhyay A, Joshi V ACS Pharmacol Transl Sci. 2024; 7(9):2573-2587.

PMID: 39296276 PMC: 11406696. DOI: 10.1021/acsptsci.4c00278.

NEDD4 and NEDD4L: Ubiquitin Ligases Closely Related to Digestive Diseases.

Xu J, Jiang W, Hu T, Long Y, Shen Y Biomolecules. 2024; 14(5).

PMID: 38785984 PMC: 11117611. DOI: 10.3390/biom14050577.

E3 ubiquitin ligase UBR5 modulates circadian rhythm by facilitating the ubiquitination and degradation of the key clock transcription factor BMAL1.

Duan C, Li Y, Zhi H, Tian Y, Huang Z, Chen S Acta Pharmacol Sin. 2024; 45(9):1793-1808.

PMID: 38740904 PMC: 11336169. DOI: 10.1038/s41401-024-01290-z.

USP26 promotes colorectal cancer tumorigenesis by restraining PRKN-mediated mitophagy.

Wu Q, Wang Z, Chen S, She X, Zhu S, Li P Oncogene. 2024; 43(21):1581-1593.

PMID: 38565942 DOI: 10.1038/s41388-024-03009-0.

Differential Proteomic Analysis of Low-Dose Chronic Paralytic Shellfish Poisoning.

Liu X, Wang F, Yu H, Liu C, Xia J, Ma Y Mar Drugs. 2024; 22(3).

PMID: 38535448 PMC: 10972186. DOI: 10.3390/md22030108.

References

Jackson P, Eldridge A, Freed E, Furstenthal L, Hsu J, Kaiser B . The lore of the RINGs: substrate recognition and catalysis by ubiquitin ligases. Trends Cell Biol. 2000; 10(10):429-39. DOI: 10.1016/s0962-8924(00)01834-1. View

Wang M, Pickart C . Different HECT domain ubiquitin ligases employ distinct mechanisms of polyubiquitin chain synthesis. EMBO J. 2005; 24(24):4324-33. PMC: 1356336. DOI: 10.1038/sj.emboj.7600895. View

Qiu L, Joazeiro C, Fang N, Wang H, Elly C, Altman Y . Recognition and ubiquitination of Notch by Itch, a hect-type E3 ubiquitin ligase. J Biol Chem. 2000; 275(46):35734-7. DOI: 10.1074/jbc.M007300200. View

Kishi N, Tang Z, Maeda Y, Hirai A, Mo R, Ito M . Murine homologs of deltex define a novel gene family involved in vertebrate Notch signaling and neurogenesis. Int J Dev Neurosci. 2001; 19(1):21-35. DOI: 10.1016/s0736-5748(00)00071-x. View

Yamamoto N, Yamamoto S, Inagaki F, Kawaichi M, Fukamizu A, Kishi N . Role of Deltex-1 as a transcriptional regulator downstream of the Notch receptor. J Biol Chem. 2001; 276(48):45031-40. DOI: 10.1074/jbc.M105245200. View

Marchese A, Benovic J . Agonist-promoted ubiquitination of the G protein-coupled receptor CXCR4 mediates lysosomal sorting. J Biol Chem. 2001; 276(49):45509-12. DOI: 10.1074/jbc.C100527200. View

Aguilar R, Wendland B . Ubiquitin: not just for proteasomes anymore. Curr Opin Cell Biol. 2003; 15(2):184-90. DOI: 10.1016/s0955-0674(03)00010-3. View

Mazaleyrat S, Fostier M, Wilkin M, Aslam H, Evans D, Cornell M . Down-regulation of Notch target gene expression by Suppressor of deltex. Dev Biol. 2003; 255(2):363-72. DOI: 10.1016/s0012-1606(02)00086-6. View

Takeyama K, Aguiar R, Gu L, He C, Freeman G, Kutok J . The BAL-binding protein BBAP and related Deltex family members exhibit ubiquitin-protein isopeptide ligase activity. J Biol Chem. 2003; 278(24):21930-7. DOI: 10.1074/jbc.M301157200. View

10.

Hu Q, Ang B, Karsak M, Hu W, Cui X, Duka T . F3/contactin acts as a functional ligand for Notch during oligodendrocyte maturation. Cell. 2003; 115(2):163-75. DOI: 10.1016/s0092-8674(03)00810-9. View

11.

Marchese A, Raiborg C, Santini F, Keen J, Stenmark H, Benovic J . The E3 ubiquitin ligase AIP4 mediates ubiquitination and sorting of the G protein-coupled receptor CXCR4. Dev Cell. 2003; 5(5):709-22. DOI: 10.1016/s1534-5807(03)00321-6. View

12.

Angers A, Ramjaun A, McPherson P . The HECT domain ligase itch ubiquitinates endophilin and localizes to the trans-Golgi network and endosomal system. J Biol Chem. 2003; 279(12):11471-9. DOI: 10.1074/jbc.M309934200. View

13.

Gupta-Rossi N, Six E, LeBail O, Logeat F, Chastagner P, Olry A . Monoubiquitination and endocytosis direct gamma-secretase cleavage of activated Notch receptor. J Cell Biol. 2004; 166(1):73-83. PMC: 2172142. DOI: 10.1083/jcb.200310098. View

14.

Bai Y, Yang C, Hu K, Elly C, Liu Y . Itch E3 ligase-mediated regulation of TGF-beta signaling by modulating smad2 phosphorylation. Mol Cell. 2004; 15(5):825-31. DOI: 10.1016/j.molcel.2004.07.021. View

15.

Fang D, Kerppola T . Ubiquitin-mediated fluorescence complementation reveals that Jun ubiquitinated by Itch/AIP4 is localized to lysosomes. Proc Natl Acad Sci U S A. 2004; 101(41):14782-7. PMC: 522008. DOI: 10.1073/pnas.0404445101. View

16.

Hori K, Fostier M, Ito M, Fuwa T, Go M, Okano H . Drosophila deltex mediates suppressor of Hairless-independent and late-endosomal activation of Notch signaling. Development. 2004; 131(22):5527-37. DOI: 10.1242/dev.01448. View

17.

Diederich R, Matsuno K, Hing H, Artavanis-Tsakonas S . Cytosolic interaction between deltex and Notch ankyrin repeats implicates deltex in the Notch signaling pathway. Development. 1994; 120(3):473-81. DOI: 10.1242/dev.120.3.473. View

18.

Johnson E, Ma P, Ota I, Varshavsky A . A proteolytic pathway that recognizes ubiquitin as a degradation signal. J Biol Chem. 1995; 270(29):17442-56. DOI: 10.1074/jbc.270.29.17442. View

19.

Matsuno K, Diederich R, Go M, Blaumueller C, Artavanis-Tsakonas S . Deltex acts as a positive regulator of Notch signaling through interactions with the Notch ankyrin repeats. Development. 1995; 121(8):2633-44. DOI: 10.1242/dev.121.8.2633. View

20.

Perry W, Hustad C, Swing D, OSullivan T, Jenkins N, Copeland N . The itchy locus encodes a novel ubiquitin protein ligase that is disrupted in a18H mice. Nat Genet. 1998; 18(2):143-6. DOI: 10.1038/ng0298-143. View