Identification of the Enzyme Required for Activation of the Small Ubiquitin-like Protein SUMO-1

Desterro, Joana; Rodríguez, Manuel Sánchez; Kemp, Graham D.; Hay, Ronald T.

doi:10.1074/jbc.274.15.10618

Cited by 319 publications

(256 citation statements)

References 35 publications

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“…37,38 SUMO-1 (also termed sentrin, GMP1, SMT3C or ULP1) is a small polypeptide that is covalently attached to PML and several other PML-NB components, including Sp100, 40 Daxx, 41 p53 42,43 and CBP, 44 through an enzymatic machinery similar to that of ubiquitin modification. 45 SUMOlation requires an activating E1 SUMO-1 activating enzyme (SAE)1/SAE2 heterodimer, 46 the conjugating E2 enzyme Ubc9 47,48 and the recently identified E3 SUMO ligases. [49][50][51][52] In contrast to ubiquitination, SUMOlation usually does not lead to protein degradation but regulates protein-protein interactions, subcellular localisation and activity.…”

Section: Pml and Its Associated Nbsmentioning

confidence: 99%

Body language: the function of PML nuclear bodies in apoptosis regulation

2003

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Promyelocytic leukaemia (PML) nuclear bodies (NBs) are macromolecular nuclear domains present in virtually every mammalian cell. PML nuclear bodies (PML-NBs) were functionally linked to various fundamental cellular processes, including transcriptional control, tumour suppression and apoptosis regulation. Supporting the important function of PML and its associated NBs in apoptosis regulation, several apoptotic regulators localise to PML-NBs, and cells from PMLdeficient mice show severe apoptotic defects, including induction of genotoxic stress and death receptor CD95 (Fas/ APO-1) activation. Based on the current literature, we hypothesise that PML-NBs regulate apoptosis through different molecular mechanisms, on the one hand by acting as macromolecular scaffolds for recruitment and post-translational modification of the apoptotic key regulator p53, and on the other by regulating the subcellular bioavailability and quality of some apoptotic signal transducers.

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Section: Pml and Its Associated Nbsmentioning

confidence: 99%

Body language: the function of PML nuclear bodies in apoptosis regulation

2003

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“…The ATP-dependent activation step in the SUMO pathway results in the formation of a high-energy thioester bond between the C-terminal Glycine residue of SUMO and an E1 enzyme, and is achieved by the dimeric Aos1/Uba2 enzyme (also called SAE1/SAE2, or Sua1/Uba2; Desterro et al, 1999;Gong et al, 1999;Okuma et al, 1999).…”

Section: E1mentioning

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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“…Smt3p, which is 48% identical to human SUMO-1, has been identified in yeast (12,13). SUMO-1͞Smt3p is activated by a heterodimeric E1 enzyme in both the yeast and mammalian systems (13)(14)(15). In addition, UBC9, an E2 enzyme, has been shown to specifically conjugate SUMO-1͞Smt3p to the target proteins (11,(16)(17)(18).…”

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SUMO-1 conjugation to topoisomerase I: A possible repair response to topoisomerase-mediated DNA damage

Mao¹,

Sun²,

Desai³

et al. 2000

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

187

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Ubiquitin͞26S proteasome-dependent degradation of topoisomerase I (TOP1) has been suggested to be a unique repair response to TOP1-mediated DNA damage. In the current study, we show that treatment of mammalian cells or yeast cells expressing human DNA TOP1 with camptothecin (CPT) induces covalent modification of the TOP1 by SUMO-1͞Smt3p, a ubiquitin-like protein. This conclusion is based on the following observations: (i) Mammalian DNA TOP1 conjugates induced by CPT were cross-reactive with SUMO-1͞Smt3p-specific antibodies both in yeast expressing human DNA TOP1 as well as mammalian cells. (ii) The formation of TOP1 conjugates was shown to be dependent on UBC9, the E2 enzyme for SUMO-1͞Smt3p. (iii) TOP1 physically interacts with UBC9. (iv) Ubc9 mutant yeast cells expressing human DNA TOP1 was hypersensitive to CPT, suggesting that UBC9͞SUMO-1 may be involved in the repair of TOP1-mediated DNA damage.UBC9 ͉ Smt3p ͉ ubiquitin T opoisomerase-mediated DNA damage represents an unique type of DNA damage whose importance has become increasingly appreciated. Many antibiotics, anticancer drugs, toxins, carcinogens, and physiological stresses are known to abort the catalytic cycles of topoisomerases resulting in the formation of topoisomerase-mediated DNA damage (1-7). Despite its importance, little is known about the molecular basis for the repair of this unique type of DNA damage.Recent studies have demonstrated that topoisomerase I-(TOP1) mediated DNA damage activates a ubiquitin͞proteasome pathway, resulting in degradation of TOP1 (down-regulation of TOP1) (8). It has been speculated that this pathway may represent a unique repair mechanism for TOP1-mediated DNA damage because down-regulation of human TOP1 (hTOP1) is expected to result in resistance͞tolerance to TOP1 poisons (8).Human SUMO-1 (small ubiquitin-like modifier) is an 11-kDa protein that shares 18% sequence homology with ubiquitin (9-11). Smt3p, which is 48% identical to human SUMO-1, has been identified in yeast (12,13). SUMO-1͞Smt3p is activated by a heterodimeric E1 enzyme in both the yeast and mammalian systems (13)(14)(15). In addition, UBC9, an E2 enzyme, has been shown to specifically conjugate SUMO-1͞Smt3p to the target proteins (11,(16)(17)(18). Recently, an enzyme Ulp1p, which specifically cleaves proteins from SUMO-1͞Smt3p conjugates and is distinct from isopeptidases for ubiquitin conjugates, also has been identified in yeast (19). These results suggest that the SUMO-1͞Smt3p pathway is very similar to the ubiquitin pathway but distinct E1 and E2 enzymes as well as proteases are involved in these pathways. The biological function of the SUMO-1͞Smt3p pathway appears diverse. UBC9 was originally identified to play an essential function in G 2 -M cell cycle progression in yeast (20). However, UBC9 is also known to be important for DNA repair (21). It has been shown that SUMO-1 can be conjugated to a number of proteins such as PML (22), RanGAP1 (23, 24), I B␣ (25), FAS͞apolipoprotein-1 (26), p53 (27, 28), RAD51, and RAD52 (29). A growing number of pr...

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Identification of the Enzyme Required for Activation of the Small Ubiquitin-like Protein SUMO-1

Cited by 319 publications

References 35 publications

Body language: the function of PML nuclear bodies in apoptosis regulation

Body language: the function of PML nuclear bodies in apoptosis regulation

SUMO: of branched proteins and nuclear bodies

SUMO-1 conjugation to topoisomerase I: A possible repair response to topoisomerase-mediated DNA damage

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