Two different stages of epidermal growth factor (EGF) receptor endocytosis are sensitive to free ubiquitin depletion produced by proteasome inhibitor MG132

Melikova, M S; Кондратов, К. А.; Корнилова, Е. С.

doi:10.1016/j.cellbi.2005.09.003

Cited by 51 publications

(63 citation statements)

References 44 publications

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“…The accumulation of unmodified TRC35 (Fig. 3A, lanes 9 and 10 vs. lanes 11 and 12) is probably due to depletion of free Ub in the cell (28). Collectively, these data support the idea that the TRC35 molecules unable to associate with Bag6 at the NLS domain become targets for Ub-dependent degradation through a client-chaperone interaction with Bag6.…”

Section: Get5supporting

confidence: 75%

Structural basis for regulation of the nucleo-cytoplasmic distribution of Bag6 by TRC35

Mock

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The metazoan protein BCL2-associated athanogene cochaperone 6 (Bag6) forms a hetero-trimeric complex with ubiquitin-like 4A and transmembrane domain recognition complex 35 (TRC35). This Bag6 complex is involved in tail-anchored protein targeting and various protein quality-control pathways in the cytosol as well as regulating transcription and histone methylation in the nucleus. Here we present a crystal structure of Bag6 and its cytoplasmic retention factor TRC35, revealing that TRC35 is remarkably conserved throughout the opisthokont lineage except at the C-terminal Bag6-binding groove, which evolved to accommodate Bag6, a unique metazoan factor. While TRC35 and its fungal homolog, guided entry of tail-anchored protein 4 (Get4), utilize a conserved hydrophobic patch to bind their respective partners, Bag6 wraps around TRC35 on the opposite face relative to the Get4-5 interface. We further demonstrate that TRC35 binding is critical not only for occluding the Bag6 nuclear localization sequence from karyopherin α to retain Bag6 in the cytosol but also for preventing TRC35 from succumbing to RNF126-mediated ubiquitylation and degradation. The results provide a mechanism for regulation of Bag6 nuclear localization and the functional integrity of the Bag6 complex in the cytosol.tail-anchor targeting | X-ray crystallography | tail-anchor recognition complex | proteasome-dependent degradation | GET pathway

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Section: Get5supporting

confidence: 75%

Structural basis for regulation of the nucleo-cytoplasmic distribution of Bag6 by TRC35

Mock

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Monensin can block Golgi transport by preventing the acidification of intercellular compartments and the internalization and recycling of receptors [24]. Serving as an inhibitor for the 26S proteasome, MG132 may deplete cells of free Ub [25], leading to reduction in the internalization of surface receptors. Western blot analysis of the lysates using GalT1p 13 antibodies showed that the GTAP-dependent decrease of long GalT1 was abrogated in the presence of both MG132 and monensin (Fig.…”

Section: Gtap Affects the Internalization Of Surface Galt1 In Escsmentioning

confidence: 99%

Characterization of a Novel Ubiquitin-Conjugating Enzyme That Regulates β1,4-Galactosyltransferase-1 in Embryonic Stem Cells

Wassler¹,

Shur

Zhou³

et al. 2008

Stem Cells

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In this study we identified a novel galactosyltransferase 1-associating protein (GTAP) by cDNA cloning from a murine embryonic cDNA library using the two-hybrid yeast system. GTAP is expressed in early embryonic tissues, as well as in adult tissues with active cell turnover, and belongs to the class III ubiquitin-conjugating (E2) enzyme family. Its COOH-terminal domain contains a consensus sequence for ubiquitin binding shared by all the ubiquitin-conjugating enzymes, whereas its NH 2 -terminal domain appears critical for the binding and internalization of cell surface galactosyltransferase 1 (GalT1) in embryonic stem cells through a monensin-and MG132-dependent pathway. We have found that GTAP regulates GalT1-associated, laminin-dependent embryonic cell adhesion and the formation of embryoid bodies. Thus, GTAP functions as an evolutionarily conserved E2 enzyme, which may participate in intercellular adhesion and embryonic development. STEM CELLS 2008;

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“…The ouabain-induced reduction of GlyT2 was completely prevented in the presence of leupeptin, a lysosomal protease inhibitor. The partial effect exerted by the proteasome inhibitor MG132 are probably the result of decreased GlyT2 ubiquitination caused by depletion of the intracellular free ubiquitin pool (Patnaik et al, 2000; Melikova et al, 2006). This conclusion is based on our earlier results showing that endocytosis and further sorting of GlyT2 to the recycling or degradation pathways in neurons depends on ubiquitination, and that the ubiquitination status of the transporter is highly sensitive to ubiquitin homeostasis (de Juan-Sanz et al, 2013).…”

Section: Ouabain Effect On the Transport Activity And Expression Of Gmentioning

confidence: 99%

Na+/K+-ATPase Is a New Interacting Partner for the Neuronal Glycine Transporter GlyT2 That Downregulates Its Expression In Vitro and In Vivo

Juan-Sanz

Núñez

Villarejo-López

et al. 2013

Journal of Neuroscience

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The neuronal glycine transporter GlyT2 plays a fundamental role in the glycinergic neurotransmission by recycling the neurotransmitter to the presynaptic terminal. GlyT2 is the main supplier of glycine for vesicle refilling, a process that is absolutely necessary to preserve quantal glycine content in synaptic vesicles. Alterations in GlyT2 activity modify glycinergic neurotransmission and may underlie several neuromuscular disorders, such as hyperekplexia, myoclonus, dystonia, and epilepsy. Indeed, mutations in the gene encoding GlyT2 are the main presynaptic cause of hyperekplexia in humans and produce congenital muscular dystonia type 2 (CMD2) in Belgian Blue cattle. GlyT2 function is strictly coupled to the sodium electrochemical gradient actively generated by the Naϩ /Cl Ϫ /glycine generating large rises of Na ϩ inside the presynaptic terminal that must be efficiently reduced by the NKA to preserve Na ϩ homeostasis. In this work, we have used high-throughput mass spectrometry to identify proteins interacting with GlyT2 in the CNS. NKA was detected as a putative candidate and through reciprocal coimmunoprecipitations and immunocytochemistry analyses the association between GlyT2 and NKA was confirmed. NKA mainly interacts with the raft-associated active pool of GlyT2, and low and high levels of the specific NKA ligand ouabain modulate the endocytosis and total expression of GlyT2 in neurons. The ouabainmediated downregulation of GlyT2 also occurs in vivo in two different systems: zebrafish embryos and adult rats, indicating that this NKA-mediated regulatory mechanism is evolutionarily conserved and may play a relevant role in the physiological control of inhibitory glycinergic neurotransmission.

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Two different stages of epidermal growth factor (EGF) receptor endocytosis are sensitive to free ubiquitin depletion produced by proteasome inhibitor MG132

Cited by 51 publications

References 44 publications

Structural basis for regulation of the nucleo-cytoplasmic distribution of Bag6 by TRC35

Structural basis for regulation of the nucleo-cytoplasmic distribution of Bag6 by TRC35

Characterization of a Novel Ubiquitin-Conjugating Enzyme That Regulates β1,4-Galactosyltransferase-1 in Embryonic Stem Cells

Na+/K+-ATPase Is a New Interacting Partner for the Neuronal Glycine Transporter GlyT2 That Downregulates Its Expression In Vitro and In Vivo

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