Membrane transport: Ubiquitylation in endosomal sorting

Dupré-Crochet, Sophie; Volland, Christiane; Haguenauer‐Tsapis, Rosine

doi:10.1016/s0960-9822(01)00558-9

Cited by 80 publications

(65 citation statements)

References 23 publications

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“…Next, we investigated whether intracellular Gliotactin vesicles were ubiquitinylated as ubiquitylation plays an important role in endocytosis, recycling and targeting of proteins for degradation (Dupre et al, 2001;Katzmann et al, 2001;Piper and Luzio, 2007;Purdy and Russell, 2007;Raiborg et al, 2002). Immunolabeling with an antibody against ubiquitin showed colabeling with internalized Gliotactin, suggesting that ubiquitylation is a part of the process of Gliotactin internalization (Fig.…”

Section: Overexpression Of Gliotactin Results In Excessive Endocytosimentioning

confidence: 99%

Control of Gliotactin localization and levels by tyrosine phosphorylation and endocytosis is necessary for survival of polarized epithelia

Barmchi

Browne

Sturgeon

et al. 2010

Journal of Cell Science

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SummaryThe tricellular junction (TCJ) forms at the convergence of bicellular junctions from three adjacent cells in polarized epithelia and is necessary for maintaining the transepithelial barrier. In the fruitfly Drosophila, the TCJ is generated at the meeting point of bicellular septate junctions. Gliotactin was the first identified component of the TCJ and is necessary for TCJ and septate junction development. Gliotactin is a member of the neuroligin family and associates with the PDZ protein discs large. Beyond this interaction, little is known about the mechanisms underlying Gliotactin localization and function at the TCJ. In this study, we show that Gliotactin is phosphorylated at conserved tyrosine residues, a process necessary for endocytosis and targeting to late endosomes and lysosomes for degradation. Regulation of Gliotactin levels through phosphorylation and endocytosis is necessary as overexpression results in displacement of Gliotactin away from the TCJ throughout the septate junction domain. Excessive Gliotactin in polarized epithelia leads to delamination, paired with subsequent migration, and apoptosis. The apoptosis and the resulting compensatory proliferation resulting from high levels of Gliotactin are mediated by the Drosophila JNK pathway. Therefore, Gliotactin levels within the cell membrane are regulated to ensure correct protein localization and cell survival.

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Section: Overexpression Of Gliotactin Results In Excessive Endocytosimentioning

confidence: 99%

Control of Gliotactin localization and levels by tyrosine phosphorylation and endocytosis is necessary for survival of polarized epithelia

Barmchi

Browne

Sturgeon

et al. 2010

Journal of Cell Science

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“…48). TSG101 is thought to recognize these monoubiquitinated proteins and to mediate their internalization (27,28,49,50). Furthermore, TSG101 is involved in virus budding.…”

Section: Discussionmentioning

confidence: 99%

TSG101 Interacts with Apoptosis-antagonizing Transcription Factor and Enhances Androgen Receptor-mediated Transcription by Promoting Its Monoubiquitination

Burgdorf¹,

Leister

Scheidtmann

2004

Journal of Biological Chemistry

102

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Apoptosis-antagonizing transcription factor (AATF), also termed Che-1, was identified as interacting protein of Dlk/ZIP kinase and RNA polymerase II, respectively. Che-1 has additionally been shown to bind Rb, thereby activating transcription factor E2F and promoting cell cycle progression. Moreover, AATF enhances steroid receptor-mediated transactivation in a hormone-and dose-dependent manner (Leister, P., Burgdorf, S., and Scheidtmann, K. H., (2003) Signal Transduction 3, 18 -25). These data suggest that AATF exerts its functions through interaction with different transcription factors. In search of novel interaction partners of AATF, we identified the tumor susceptibility gene product TSG101, which had also been recognized as a co-regulator of nuclear hormone receptors. Interestingly, TSG101 and AATF functioned as cooperative coactivators in androgen receptor-mediated transcription. Because TSG101 was also shown to play a role in regulation of ubiquitin conjugation, we asked whether its coactivating function might be linked to ubiquitination. Indeed, TSG101 enhanced monoubiquitination of the androgen receptor in a ligand-dependent manner, and this correlated with enhanced transactivating capacity. Furthermore, a dominant-negative mutant of ubiquitin preventing polyubiquitination also stimulated androgen receptor-mediated transcription, which in this case could not be enhanced by TSG101. We propose that TSG101 activates androgen receptor-induced transcription by transient stabilization of the monoubiquitinated state, thus revealing a novel regulatory mechanism for nuclear receptors. Apoptosis-antagonizing transcription factor (AATF)1 was first identified as a protein interaction partner of Dlk/ZIP kinase (1). Dlk/ZIP kinase, in turn, is a member of the deathassociated protein kinase family that plays a role in different processes like apoptosis (reviewed in Ref.2) and mitosis (3). AATF was shown to interfere with Dlk-induced apoptosis, thus explaining its name (1). AATF is conserved from yeast to man, suggesting that it fulfills an important function. Indeed, the mouse ortholog (termed traube) has been shown to play an essential role in early embryogenesis (4). Moreover, the human ortholog of AATF (termed Che-1) was independently identified as an interacting protein of the RNA polymerase II, subunit 11, and the tumor-suppressor protein Rb (5). This latter interaction releases the repression function of Rb on E2F-mediated transcription, presumably by displacing histone deacetylase-1 from the Rb⅐E2F complex, thereby promoting cell cycle progression (6). Thus, AATF/Che-1 appears to play a role in cell cycle control. Consistent with this assumption is its down-regulation upon TGF-␤-induced differentiation (7).The AATF protein has a modular structure. At its N terminus it contains an acidic region that is characteristic of several transcription factors, such as VP16 or BRCA-1. In its C-terminal half, it contains three highly conserved regions, the significance of which is not known. Furthermore, AATF contains a leu...

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“…Although certain Ub-dependent functions involve the formation of long polyubiquitin chains, MVB targeting does not; the fusion of a single Ub is sufficient to direct ILV targeting, and there are few long polyubiquitin chains on MVB cargo proteins (Hicke & Dunn 2003, Dupre et al 2001. Many efficiently downregulated proteins are modified by several Ubs, yet these either are linked directly to substrate proteins via several lysine residues (multiple monoubiqitination) (Haglund et al 2003) or may be present in short oligo-Ub chains consisting of lysine 63 (K63)-linked Ubs (Hicke & Dunn 2003, Dupre et al 2001.…”

Section: Lumen Ubiquitin As a Sorting Signalmentioning

confidence: 99%

Biogenesis and Function of Multivesicular Bodies

Piper

Katzmann

2007

Annu. Rev. Cell Dev. Biol.

664

660

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The two major cellular sites for membrane protein degradation are the proteasome and the lysosome. Ubiquitin attachment is a sorting signal for both degradation routes. For lysosomal degradation, ubiquitination triggers the sorting of cargo proteins into the lumen of late endosomal multivesicular bodies (MVBs)/endosomes. MVB formation occurs when a portion of the limiting membrane of an endosome invaginates and buds into its own lumen. Intralumenal vesicles are degraded when MVBs fuse to lysosomes. The proper delivery of proteins to the MVB interior relies on specific ubiquitination of cargo, recognition and sorting of ubiquitinated cargo to endosomal subdomains, and the formation and scission of cargo-filled intralumenal vesicles. Over the past five years, a number of proteins that may directly participate in these aspects of MVB function and biogenesis have been identified. However, major questions remain as to exactly what these proteins do at the molecular level and how they may accomplish these tasks.

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Membrane transport: Ubiquitylation in endosomal sorting

Cited by 80 publications

References 23 publications

Control of Gliotactin localization and levels by tyrosine phosphorylation and endocytosis is necessary for survival of polarized epithelia

Control of Gliotactin localization and levels by tyrosine phosphorylation and endocytosis is necessary for survival of polarized epithelia

TSG101 Interacts with Apoptosis-antagonizing Transcription Factor and Enhances Androgen Receptor-mediated Transcription by Promoting Its Monoubiquitination

Biogenesis and Function of Multivesicular Bodies

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