Ubc9 Is Essential for Viability of Higher Eukaryotic Cells

Hayashi, Tomoko; Seki, Masayuki; Maeda, Daisuke; Wang, Wensheng; Kawabe, Yoh Ichi; Seki, Takahiko; Saitoh, Hisato; Fukagawa, Tatsuo; Yagi, Hideki; Enomoto, Takemi

doi:10.1006/excr.2002.5634

Cited by 107 publications

(92 citation statements)

References 45 publications

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“…The high stability of maternal Ubc9 protein is consistent with data obtained for other maternally supplied zebrafish proteins (Ryu et al, 2005;Plaster et al, 2006). In addition, it is consistent with data obtained for Ubc9 in a chick cell line (Hayashi et al, 2002), where Ubc9 protein was still detectable 2 d after gene inactivation, and sumoylated proteins could even be seen for 1 additional day (Hayashi et al, 2002).…”

Section: The Stability Of Ubc9 Protein and The Kinetics Of Phenotype supporting

confidence: 89%

“…Comparably late apoptosis is only observed much later than the defects during cell cycle progression, suggesting that here cell viability might dependent on another function of Ubc9. Comparably late apoptosis is also seen in Ubc9-deficient chick cell line where cell death coincides with the loss of sumoylated Ran-GAP1, a factor needed for nuclear import of proteins (Hayashi et al, 2002). Similarly, in Ubc9 knock out mice, mislocalization of RanGAP1 and loss of nuclear integrity were proposed to be likely reasons for the observed cell death (Nacerddine et al, 2005).…”

Section: Ubc9 Is Required For Tissue-specific Cell Viabilitymentioning

confidence: 98%

“…In vertebrates, the impact of sumoylation on developmental programs is even less clear. Inducible loss of Ubc9 function in a chick cell line leads to polynucleated cells and cell cycle-independent apoptosis (Hayashi et al, 2002), whereas in mouse embryos, loss of Ubc9 causes chromosome mis-segregation and loss of nuclear integrity (Nacerddine et al, 2005). These defects result in early lethality of mutant embryos, preventing analyses to address possible roles of Ubc9 during later developmental processes.…”

Section: Introductionmentioning

confidence: 99%

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Ubc9 Regulates Mitosis and Cell Survival during Zebrafish Development

Nowak

Hammerschmidt

2006

MBoC

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Many proteins are modified by conjugation with Sumo, a gene-encoded, ubiquitin-related peptide, which is transferred to its target proteins via an enzymatic cascade. A central component of this cascade is the E2-conjugating enzyme Ubc9, which is highly conserved across species. Loss-of-function studies in yeast, nematode, fruit fly, and mouse blastocystes point to multiple roles of Ubc9 during cell cycle regulation, maintenance of nuclear architecture, chromosome segregation, and viability. Here we show that in zebrafish embryos, reduction of Ubc9 activity by expression of a dominant negative version causes widespread apoptosis, similar to the effect described in Ubc9-deficient mice. However, antisense-based knock down of zygotic ubc9 leads to much more specific defects in late proliferating tissues, such as cranial cartilage and eyes. Affected cartilaginous elements are of relatively normal size and shape, but consist of fewer and larger cells.

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Section: The Stability Of Ubc9 Protein and The Kinetics Of Phenotype supporting

confidence: 89%

Section: Ubc9 Is Required For Tissue-specific Cell Viabilitymentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Ubc9 Regulates Mitosis and Cell Survival during Zebrafish Development

Nowak

Hammerschmidt

2006

MBoC

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“…Consistent with this, several genes encoding SUMO-conjugating enzymes and SUMO proteases are also essential (22,42,52,53). Sumoylation is also likely to be an essential cellular process for higher eukaryotic cells because Ubc9 is required for the viability of chicken DT40 cells (54).…”

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confidence: 66%

A Proteomic Study of SUMO-2 Target Proteins

Vertegaal

Ogg

Jaffray

et al. 2004

Journal of Biological Chemistry

209

164

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The SUMO family in vertebrates includes at least three distinct proteins (SUMO-1, -2, and -3) that are added as post-translational modifications to target proteins. A considerable number of SUMO-1 target proteins have been identified, but little is known about SUMO-2. A stable HeLa cell line expressing His 6 -tagged SUMO-2 was established and used to label and purify novel endogenous SUMO-2 target proteins. Tagged forms of SUMO-2 were functional and localized predominantly in the nucleus. His 6 -tagged SUMO-2 conjugates were affinity-purified from nuclear fractions and identified by mass spectrometry. Eight novel potential SUMO-2 target proteins were identified by at least two peptides. Three of these proteins, SART1, heterogeneous nuclear ribonucleoprotein (RNP) M, and the U5 small nuclear RNP 200-kDa helicase, play a role in RNA metabolism. SART1 and heterogeneous nuclear RNP M were both shown to be genuine SUMO targets, confirming the validity of the approach.The small ubiquitin-like modifier (SUMO) 1 is linked to target proteins by post-translational conjugation and may thereby influence protein function and/or localization (1-3). The name derives from the relationship of SUMO to the better characterized post-translational modifier ubiquitin (4). They are 18% identical at the amino acid level and show a clear similarity in their respective three-dimensional structures (5). Whereas yeast and nematodes have a single SUMO gene, in humans and mice, the SUMO family consists of three members, SUMO-1, -2, and -3, which are encoded by separate genes. The mature forms of SUMO-2 and SUMO-3 are similar (ϳ95% identical), but less closely related to SUMO-1 (ϳ50% identical) (6 -8).Despite their close similarity, there is evidence that SUMO-1 and SUMO-2/3 are preferentially conjugated to distinct sets of target proteins. Whereas RanGAP1 is modified by SUMO-1, many as yet unidentified proteins are modified by SUMO-2/3 after exposure of cells to various stress stimuli (7).Several groups independently identified SUMO-1, which is also known as PIC1, GMP1, SMT3C, UBL1, and sentrin (9 -13). In contrast to most polyubiquitinylated proteins, sumoylated proteins are not thereby targeted for degradation. SUMO-1 can even compete with ubiquitin for the same acceptor lysine in the target protein. In the case of IB␣, SUMO modification serves to protect the protein from ubiquitin-mediated degradation (14), whereas in yeast, DNA repair can proceed only after proliferating cell nuclear antigen is desumoylated to allow ubiquitination. Here, ubiquitination does not target the protein for degradation, but functions as a switch to activate the DNA repair function of proliferating cell nuclear antigen (15). Therefore, despite their structural relationship, it appears that SUMO and ubiquitin conjugation can play distinct roles in modulating target proteins. Sumoylation can also regulate the subcellular localization of target proteins. For example, SUMO conjugation is required for both the nuclear pore and kinetochore localization of RanGAP1 (1...

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“…Bien que la séquence primaire de SUMO soit différente de celle de l'ubiquitine, la structure tridimensionnelle de ces deux protéines est similaire (Figure 1). La sumoylation est un processus essentiel puisque l'invalidation des enzymes de la sumoylation est délétère pour les cellules eucaryotes [2,3]. Le terme SUMO regroupe une famille de 4 protéines (SUMO1-4), formées chacune d'environ 100 résidus.…”

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Nouvelles fonctions extranucléaires de la sumoylation des protéines dans le système nerveux central

Martin

2009

Med Sci (Paris)

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La modification post-traductionnelle des protéines est un processus enzymatique qui consiste en l'ajout de groupements chimiques, de sucres, de lipides ou encore de polypeptides après la synthèse protéique. Ces modifications peuvent altérer la conformation des protéines, influer sur leur localisation cellulaire, dicter leur stabilité ou encore agir sur leur activité et donc sur leur fonction physiologique. Par exemple, les processus synaptiques de la communication neuronale sont particulièrement complexes et finement régulés, en partie grâce à ces modifications post-traductionnelles. La sumoylation est une modification post-traductionnelle dont les fonctions en dehors du noyau sont peu connues. Cette synthèse fait le point sur notre connaissance des fonctions extranucléaires de la sumoylation dans le système nerveux central et discute leur implication dans les maladies neurodégénératives. Qu'est-ce que la sumoylation ?La sumoylation a été découverte en 1996 [1]. C'est un processus enzymatique qui consiste en l'attachement covalent d'une protéine appelée SUMO (small ubiquitinlike modifier) sur la lysine de la séquence consensus ΨKxD/E d'une protéine cible (Ψ, acide aminé hydrophobe ; K, lysine modifiée ; x, résidu quelconque et D/E, aspartate ou glutamate). Il faut cependant noter que la littérature rapporte un nombre de plus en plus élevé de protéines sumoylées sur des lysines n'appartenant pas à un site consensus de sumoylation. Bien que la séquence primaire de SUMO soit différente de celle de l'ubiquitine, la structure tridimensionnelle de ces deux protéines est similaire (Figure 1). La sumoylation est un processus essentiel puisque l'invalidation des enzymes de la sumoylation est délétère pour les cellules eucaryotes [2,3]. Le terme SUMO regroupe une famille de 4 protéines (SUMO1-4), formées chacune d'environ 100 résidus. Les formes SUMO1-3 sont exprimées dans le cerveau alors que l'expression de SUMO-4 semble restreinte aux cellules des reins, de la rate et des ganglions lymphatiques. SUMO-2 et SUMO-3 ne diffèrent que par 3 résidus et ne présentent que 47 % d'homologie avec SUMO-1. De manière très intéressante, SUMO-2 et 3 peuvent former des chaînes de poly-SUMO, contrairement à SUMO-1 qui ne comporte pas le résidu de lysine indispensable à la formation de ces chaînes [4]. > Les modifications post-traductionnelles de protéines sont essentielles à la régulation de leur fonction et, par conséquent, au maintien de l'intégrité cellulaire. Ces modifications interviennent à tous les niveaux de la communication entre les neurones du système nerveux central. La sumoylation est une modification post-traductionnelle qui crée une liaison covalente entre une lysine de la protéine cible et une petite protéine appelée SUMO. C'est un processus réversible qui fait intervenir des enzymes spécifiques. La sumoylation est un processus régulateur fonctionnel bien connu de l'activité nucléaire et il est maintenant clairement établi que dans les neurones, il assure également un rôle majeur pour de nombreux processus extranucléai-r...

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Ubc9 Is Essential for Viability of Higher Eukaryotic Cells

Cited by 107 publications

References 45 publications

Ubc9 Regulates Mitosis and Cell Survival during Zebrafish Development

Ubc9 Regulates Mitosis and Cell Survival during Zebrafish Development

A Proteomic Study of SUMO-2 Target Proteins

Nouvelles fonctions extranucléaires de la sumoylation des protéines dans le système nerveux central

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