A New SUMO-1-specific Protease, SUSP1, That Is Highly Expressed in Reproductive Organs

Kim, Keun Il; Baek, Sung Hee; Jeon, Young Joo; Nishimori, Shigeki; Suzuki, Toshiaki; Uchida, Sanae; Shimbara, Naoki; Saitoh, Hisato; Tanaka, Keiji; Chung, Chin Ha

doi:10.1074/jbc.275.19.14102

Cited by 133 publications

(124 citation statements)

References 24 publications

(34 reference statements)

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“…This core domain contains the active site triad of the adenovirus protease, composed of residues His 54 , Glu 71 , and Cys 122 , which in the crystal structure of this enzyme have a spatial disposition identical to that of the catalytic triad of the classical cysteine protease papain (35), although the sequential order of the residues in the polypeptide chain of this enzyme is Cys 25 , His 159 , and Asn 175 . In addition, a fourth residue, Gln 115 , of the adenovirus protease is in an equivalent spatial position to the Gln 19 of papain involved in the formation of the oxyanion hole in the active site. The ASFV protein pS273R conserves the His, Cys, and Gln residues, and, as in the case of papain, has an Asn at the position of the adenovirus protease Glu 71 residue.…”

Section: Characterization Of Protein Ps273r As a Cysteine Protease-asmentioning

confidence: 99%

“…Since the publication of this report, other SUMO-1-specific proteases similar to the yeast enzyme have been identified in vertebrates (17)(18)(19). These proteases would regulate the SUMO-1-modified state of certain proteins whose function in a variety of cellular processes, such as cell cycle progression and nuclear import, is dependent on this modification (20).…”

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confidence: 99%

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African Swine Fever Virus Protease, a New Viral Member of the SUMO-1-specific Protease Family

Andrés¹,

Alejo²,

Simón‐Mateo³

et al. 2001

Journal of Biological Chemistry

107

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African swine fever virus (ASFV) is a complex DNA virus that employs polyprotein processing at Gly-GlyXaa sites as a strategy to produce several major core components of the viral particle. The virus gene S273R encodes a 31-kDa protein that contains a "core domain" with the conserved catalytic residues characteristic of SUMO-1-specific proteases and the adenovirus protease. Using a COS cell expression system, it was found that protein pS273R is capable of cleaving the viral polyproteins pp62 and pp220 in a specific way giving rise to the same intermediates and mature products as those produced in ASFV-infected cells. Furthermore, protein pS273R, like adenovirus protease and SUMO-1-specific enzymes, is a cysteine protease, because its activity is abolished by mutation of the predicted catalytic histidine and cysteine residues and is inhibited by sulfhydryl-blocking reagents. Protein pS273R is expressed late after infection and is localized in the cytoplasmic viral factories, where it is found associated with virus precursors and mature virions. In the virions, the protein is present in the core shell, a domain where the products of the viral polyproteins are also located. The identification of the ASFV protease will allow a better understanding of the role of polyprotein processing in virus assembly and may contribute to our knowledge of the emerging family of SUMO-1-specific proteases.Positive strand RNA viruses and retroviruses encode polyproteins, which are proteolytically cleaved by viral proteases to yield the nonstructural and structural proteins required for replication and morphogenesis (1-3). On the other hand, DNA viruses, such as adenoviruses and poxviruses, synthesize precursor proteins whose maturation by proteolytic removal of terminal peptides plays an essential role in virion formation (1).African swine fever virus (ASFV), 1 a large and complex virus containing a 170-kb double-stranded DNA molecule with 151 potential genes (4, 5), is atypical among DNA viruses in that it encodes two polyproteins, pp220 and pp62, which are cleaved to produce six major structural components of the virus particle (6, 7). These proteins, p150, p37, p34, and p14, derived from polyprotein pp220 and p35 and p15, products of polyprotein pp62, are the major components of the core shell, a thick protein layer that surrounds the DNA-containing central nucleoid and that is enwrapped by the inner lipoprotein envelope and the icosahedral capsid (8).2 All the proteolytic cleavages occur after the second Gly of the consensus sequence Gly-GlyXaa, which is also recognized as a cleavage site in the maturation of adenovirus structural proteins and in some cellular proteins, including polyubiquitin (9) and ubiquitin-like proteins (10). A similar cleavage site (Ala-Gly-Xaa) is used for the maturation of vaccinia virus structural proteins (11,12). Although the adenovirus protease that processes at Gly-Gly-Xaa sites is well characterized (13-15), the enzymes involved in the processing of the ASFV polyproteins or in the cleavage of vaccin...

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Section: Characterization Of Protein Ps273r As a Cysteine Protease-asmentioning

confidence: 99%

mentioning

confidence: 99%

African Swine Fever Virus Protease, a New Viral Member of the SUMO-1-specific Protease Family

Andrés¹,

Alejo²,

Simón‐Mateo³

et al. 2001

Journal of Biological Chemistry

107

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“…Since then, numerous additional enzymes have been isolated from yeasts and mammalian cells. (Li and Hochstrasser, 2000;Suzuki et al, 1999;Gong et al, 2000b;Nishida et al, 2000;Kim et al, 2000;Schwienhorst et al, 2000). These have been variously called SENPs (for`Sentrin-speci®c protease'; Gong et al, 2000b;Yeh et al, 2000), SUSPs (SUMOspeci®c protease; Kim et al, 2000) or SMT3IP1 (Nishida et al, 2000).…”

Section: Ulp (Senps/susps)mentioning

confidence: 99%

SUMO: of branched proteins and nuclear bodies

2001

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SUMO belongs to a growing number of ubiquitin-like proteins that covalently modify their target proteins. Although some evidence supports a role of SUMO modi®cation in regulating protein stability, most studied examples support a model by which SUMO alters the interaction properties of its targets, often a ecting their subcellular localization behavior. Examination of the PML nuclear bodies, whose principal components are SUMO-modi®ed, has revealed this modi®cation to be essential for their structural and functional integrity. This and other examples thus support the view that SUMO regulates the stability not of individual proteins, but rather that of entire multiprotein complexes. Oncogene (2001) 20, 7243 ± 7249.

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“…4 Several members of SUMOspecific proteases have been reported in the mammalian system. [5][6][7][8][9][10] SENP1 is a protease that appears to deconjugate a large number of sumoylated proteins. 5 Different members of these SUMO-specific proteases appear to localize in different cellular compartments where they regulate protein function by modifying the protein stability, cellular localization, and protein-protein interactions.…”

mentioning

confidence: 99%

SENP1 mediates TNF-induced desumoylation and cytoplasmic translocation of HIPK1 to enhance ASK1-dependent apoptosis

Luo

et al. 2008

Cell Death Differ

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We have previously shown that tumor necrosis factor (TNF)-induced desumoylation and subsequent cytoplasmic translocation of HIPK1 are critical for ASK1-JNK activation. However, the mechanism by which TNF induces desumoylation of HIPK1 is unclear. Here, we show that SENP1, a SUMO-specific protease, specifically deconjugates SUMO from HIPK1 in vitro and in vivo. In resting endothelial cells (ECs), SENP1 is localized in the cytoplasm where it is complexed with an antioxidant protein thioredoxin. TNF induces the release of SENP1 from thioredoxin as well as nuclear translocation of SENP1. TNF-induced SENP1 nuclear translocation is specifically blocked by antioxidants such as N-acetyl-cysteine, suggesting that TNF-induced translocation of SENP1 is ROS dependent. TNF-induced nuclear import of SENP1 kinetically correlates with HIPK1 desumoylation and cytoplasmic translocation. Furthermore, the wild-type form of SENP1 enhances, whereas the catalyticinactive mutant form or siRNA of SENP1 blocks, TNF-induced desumoylation and cytoplasmic translocation of HIPK1 as well as TNF-induced ASK1-JNK activation. More importantly, these critical functions of SENP1 in TNF signaling were further confirmed in mouse embryonic fibroblast cells derived from SENP1-knockout mice. We conclude that SENP1 mediates TNF-induced desumoylation and translocation of HIPK1, leading to an enhanced ASK1-dependent apoptosis. The small ubiquitin-like modifier (SUMO) can be covalently attached to a large number of proteins through the formation of isopeptide bonds with specific lysine residues of target proteins. 1,2 A large number of sumoylated proteins, including RanGAP1, PML, homeodomain-interacting protein kinases (HIPKs), IkB, p53, c-Jun, Sp3, Elk-1, p300 histone acetyltransferase, histone deacetylase (HDAC), and many nuclear receptors, have been identified. 1-3 Sumoylation is a dynamic process that is mediated by activating, conjugating, and ligating enzymes and that is readily reversed by a family of SUMO-specific proteases. 4 Several members of SUMOspecific proteases have been reported in the mammalian system. 5-10 SENP1 is a protease that appears to deconjugate a large number of sumoylated proteins. 5 Different members of these SUMO-specific proteases appear to localize in different cellular compartments where they regulate protein function by modifying the protein stability, cellular localization, and protein-protein interactions. 5,6,[8][9][10][11][12] However, it is not known how these SUMO-specific proteases are regulated.HIPK1 is one of three closely related serine/threonine protein kinases that are primarily localized in the nucleus where it is sumoylated. 13,14 The HIPKs were originally identified as nuclear protein kinases that function as co-repressors for various homeodomain-containing transcription factors. 15 Recently, HIPKs have been shown to interact with other proteins involved in apoptosis and signal transduction in a cellular localization-dependent manner. In nucleus, HIPK2 phosphorylates p53 on Ser 46, resulting in the activatio...

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A New SUMO-1-specific Protease, SUSP1, That Is Highly Expressed in Reproductive Organs

Cited by 133 publications

References 24 publications

African Swine Fever Virus Protease, a New Viral Member of the SUMO-1-specific Protease Family

African Swine Fever Virus Protease, a New Viral Member of the SUMO-1-specific Protease Family

SUMO: of branched proteins and nuclear bodies

SENP1 mediates TNF-induced desumoylation and cytoplasmic translocation of HIPK1 to enhance ASK1-dependent apoptosis

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