Siah-1 binds and regulates the function of Numb

Susini, Laurent; Passer, Brent J.; Amzallag-Elbaz, Nathalie; Juven‐Gershon, Tamar; Prieur, Sylvie; Privat, Nicolas; Tuynder, Marcel; Gendron, Marie‐Claude; Israël, Alain; Amson, Robert; Oren, Moshe; Telerman, Adam

doi:10.1073/pnas.261571998

Cited by 89 publications

(70 citation statements)

References 45 publications

(67 reference statements)

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“…Other functions of siah-1 involve regulation of cell cycle and pro-survival proteins through protein degradation (22,24,49,52). Whether inhibition of high glucose-induced cell death of Müller cells by siah-1 knockdown results from the inhibition of these alternative functions of siah-1 is not known.…”

Section: Discussionmentioning

confidence: 99%

siah-1 Protein Is Necessary for High Glucose-induced Glyceraldehyde-3-phosphate Dehydrogenase Nuclear Accumulation and Cell Death in Müller Cells

Yego

Mohr

2010

Journal of Biological Chemistry

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The translocation and accumulation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the nucleus has closely been associated with cell death induction. However, the mechanism of this process has not been completely understood. The E3 ubiquitin ligase siah-1 (seven in absentia homolog 1) has recently been identified as a potential shuttle protein to transport GAPDH from the cytosol to the nucleus. Previously, we have demonstrated that elevated glucose levels induce GAPDH nuclear accumulation in retinal Müller cells. Therefore, this study investigated the role of siah-1 in high glucose-induced Several reports have demonstrated that the nuclear translocation and accumulation of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) 2 play important roles in early events leading to cell death initiation and execution (1, 2). Consequently, GAPDH nuclear accumulation has been suggested to participate in the development of various degenerative diseases including diabetic retinopathy (1, 3-9, 11). Induction of GAPDH nuclear translocation and accumulation has been linked to the formation of oxidative stress and production of pro-inflammatory stimuli, such as nitric oxide and cytokines (2,(11)(12)(13)(14)(15)(16).Although some events and stimuli leading to GAPDH nuclear accumulation have been identified, the mechanism of movement of GAPDH from the cytosol to the nucleus is unclear. GAPDH lacks a common nuclear localization signal (NLS) and therefore cannot enter the nucleus by itself because of its size. A recent study has identified the E3 ubiquitin ligase siah-1 (seven in absentia homolog 1) as a potential carrier/shuttle protein (13). According to this study, GAPDH binds the NLS-bearing siah-1, forming a complex subsequently promoting translocation of GAPDH from the cytosol to the nucleus. It is postulated that the NLS on siah-1 facilitates the nuclear movement of the complex.siah-1 proteins are human homologs of the evolutionarily conserved Drosophila, E3 ubiquitin ligase sina (seven in absentia) protein (17). sina was first identified as a key protein during R7 photoreceptor development in the Drosophila fruit fly whereby it facilitates the degradation of the transcriptional repressor of neuronal fate tramtrack (TTK88) (18 -20). Follow-up studies have identified functions for siah-1 in various cellular processes including mitosis, neuronal plasticity, development, angiogenesis, inflammation, and cell death (13, 17, 20 -29). Two siah genes, siah-1 and siah-2 are present in humans and rats, whereas mice have three siah genes: siah-1a, siah-1b, and siah-2 (17, 30, 31). siah-1a and siah-1b have 98% sequence homology. Structurally, siah-1 contains an N-terminal RING domain that facilitates the ligase function, two cysteine-rich zinc finger domains, and a substrate-binding domain, which is localized on the C-terminal of the protein (27,32,33). The last 12 amino acids on the C-terminal in the substrate-binding domain are necessary for GAPDH-siah-1 interaction (13). The NLS motif is also located in the ...

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Section: Discussionmentioning

confidence: 99%

siah-1 Protein Is Necessary for High Glucose-induced Glyceraldehyde-3-phosphate Dehydrogenase Nuclear Accumulation and Cell Death in Müller Cells

Yego

Mohr

2010

Journal of Biological Chemistry

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“…Several substrates of the Siah/SINA proteins have been identified and most have been shown to be degraded in an Ub-dependent fashion. Among the substrates are key transcription factors but also cytoplasmic and membrane proteins (Susini et al, 2001;Habelhah et al, 2004;Kim et al, 2004).…”

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confidence: 99%

Seven in Absentia Proteins Affect Plant Growth and Nodulation inMedicago truncatula

et al. 2008

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Protein ubiquitination is a posttranslational regulatory process essential for plant growth and interaction with the environment. E3 ligases, to which the seven in absentia (SINA) proteins belong, determine the specificity by selecting the target proteins for ubiquitination. SINA proteins are found in animals as well as in plants, and a small gene family with highly related members has been identified in the genome of rice (Oryza sativa), Arabidopsis (Arabidopsis thaliana), Medicago truncatula, and poplar (Populus trichocarpa). To acquire insight into the function of SINA proteins in nodulation, a dominant negative form of the Arabidopsis SINAT5 was ectopically expressed in the model legume M. truncatula. After rhizobial inoculation of the 35S:SINAT5DN transgenic plants, fewer nodules were formed than in control plants, and most nodules remained small and white, a sign of impaired symbiosis. Defects in rhizobial infection and symbiosome formation were observed by extensive microscopic analysis. Besides the nodulation phenotype, transgenic plants were affected in shoot growth, leaf size, and lateral root number. This work illustrates a function for SINA E3 ligases in a broad spectrum of plant developmental processes, including nodulation.

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“…In mice, there are three highly homologous Siah proteins, Siah1A, Siah1B, and Siah 2 (12). Siahs are known to recognize several target proteins including Deleted in Colorectal Cancer (DCC), synaptophysin, and Numb and promote the degradation of these proteins (13)(14)(15).…”

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confidence: 99%

Seven in absentia homolog 1A mediates ubiquitination and degradation of group 1 metabotropic glutamate receptors

Moriyoshi

Iijima

Fujii

et al. 2004

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

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Seven in absentia homolog 1A (Siah1A) is a member of the RING-finger-containing E3 ubiquitin ligases and has been shown to bind to the Siah-interacting domain (SID) at the carboxyl-terminal tails of the long splice forms of group 1 metabotropic glutamate receptors (mGluR1a and mGluR5). We examined the function of Siah1A in ubiquitination and degradation of group 1 mGluRs in heterologously expressing cell lines. Coexpression of Siah1A markedly decreased the SID-containing splice forms of group 1 mGluRs but not the SID-lacking mGluR1b splice form or the SID-deleted mGluR1a mutant. The decrease of mGluR1a resulted from accelerated protein turnover, as revealed by pulse-chase experiments. The Siah1A-mediated degradation of group 1 mGluRs was abrogated by not only mutations at the RING-finger domain of Siah1A but also treatment with a proteasome inhibitor. Siah1A coexpression induced strong ubiquitination of group 1 mGluRs. Replacements of lysine residues with arginine showed that Siah1A-mediated ubiquitination occurs at multiple lysine residues spanning both the seven-transmembrane region and carboxyl-terminal tail of mGluR5. In situ hybridization histochemistry showed a widespread distribution of Siah1 mRNAs, with high expression in the hippocampal pyramidal neurons and cerebellar Purkinje cells. Group 1 mGluRs play critical roles in the neural plasticity in both the hippocampal neurons and Purkinje cells. This investigation indicates that Siah1A serves as a selective ubiquitin ligase that mediates ubiquitination-dependent degradation of long splice variants of group 1 mGluRs and would contribute to posttranslational down-regulation of group 1 mGluRs.

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Siah-1 binds and regulates the function of Numb

Cited by 89 publications

References 45 publications

siah-1 Protein Is Necessary for High Glucose-induced Glyceraldehyde-3-phosphate Dehydrogenase Nuclear Accumulation and Cell Death in Müller Cells

siah-1 Protein Is Necessary for High Glucose-induced Glyceraldehyde-3-phosphate Dehydrogenase Nuclear Accumulation and Cell Death in Müller Cells

Seven in Absentia Proteins Affect Plant Growth and Nodulation inMedicago truncatula

Seven in absentia homolog 1A mediates ubiquitination and degradation of group 1 metabotropic glutamate receptors

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