SUMO-specific proteases: a twist in the tail

Hay, Ronald T.

doi:10.1016/j.tcb.2007.08.002

Cited by 252 publications

(258 citation statements)

References 69 publications

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“…Several SUMO/Sentrin specific peptidases (SENP) have been cloned recently and these studies showed that each SENP shows different subcellular localization (Hay 2007). SENP2 and SENP7 are involved in the BCL6 complex (Miles et al 2005), and we found that SENP2 but not SENP7 was located in nuclear speckles.…”

Section: Bcl11a Recruits Sumo1 Into Its Nuclear Bodymentioning

confidence: 62%

BCL11A is a SUMOylated protein and recruits SUMO‐conjugation enzymes in its nuclear body

Kuwata

Nakamura

2008

Genes to Cells

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BCL11A/EVI9 is a zinc‐finger protein predominantly expressed in brain and hematopoietic cells. Previous studies show that BCL11A is involved in acute myelomonocytic leukemia and chronic lymphoid leukemia in mouse and human, respectively. Moreover, BCL11A is localized in the characteristic nuclear body in which BCL6 is co‐localized. However, the significance of BCL11A in leukemogenesis and nuclear function remains unknown. In this study we show that BCL11A interacts with UBC9, a small ubiquitin‐like modifier (SUMO) E2 conjugating enzyme, and recruits SUMO1 into the nuclear body. A lysine residue at amino acid 634 of BCL11A is SUMOylated but not required for the SUMO1 recruitment. The N‐terminal region of BCL11A is responsible for SUMO1 recruitment as well as its nuclear body formation. We also show that SENP2, a SUMO specific peptidase, is co‐localized in the nuclear body. These results suggest that BCL11A could be involved in the SUMO conjugation system, and that BCL11A might play an important role in protein modification.

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Section: Bcl11a Recruits Sumo1 Into Its Nuclear Bodymentioning

confidence: 62%

BCL11A is a SUMOylated protein and recruits SUMO‐conjugation enzymes in its nuclear body

Kuwata

Nakamura

2008

Genes to Cells

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“…Furthermore, conjugation with SUMO2/3 is known to exert at least one potentially different effect on the target from that exerted by SUMO1 conjugation, namely, the formation of SUMO2/3 chains followed by the recognition of the poly-SUMOylated target by SUMO-dependent ubiquitin ligases that polyubiquitinylate it and direct it toward proteasomal degradation, as previously reviewed (50)(51)(52). Therefore, it was relevant to characterize whether NS1 could be equally SUMOylated by the two main types of SUMO proteins in the cell.…”

Section: Pr8mentioning

confidence: 99%

SUMOylation Affects the Interferon Blocking Activity of the Influenza A Nonstructural Protein NS1 without Affecting Its Stability or Cellular Localization

Santos

Pal

Chacon

et al. 2013

J Virol

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Our pioneering studies on the interplay between the small ubiquitin-like modifier (SUMO) and influenza A virus identified the nonstructural protein NS1 as the first known SUMO target of influenza virus and one of the most abundantly SUMOylated influenza virus proteins. Here, we further characterize the role of SUMOylation for the A/Puerto Rico/8/1934 (PR8) NS1 protein, demonstrating that NS1 is SUMOylated not only by SUMO1 but also by SUMO2/3 and mapping the main SUMOylation sites in NS1 to residues K219 and K70. Furthermore, by using SUMOylatable and non-SUMOylatable forms of NS1 and an NS1-specific artificial SUMO ligase (ASL) that increases NS1 SUMOylation ϳ4-fold, we demonstrate that SUMOylation does not affect the stability or cellular localization of PR8 NS1. However, NS1's ability to be SUMOylated appears to affect virus multiplication, as indicated by the delayed growth of a virus expressing the non-SUMOylatable form of NS1 in the interferon (IFN)-competent MDCK cell line. Remarkably, while a non-SUMOylatable form of NS1 exhibited a substantially diminished ability to neutralize IFN production, increasing NS1 SUMOylation beyond its normal levels also exerted a negative effect on its IFN-blocking function. This observation indicates the existence of an optimal level of NS1 SUMOylation that allows NS1 to achieve maximal activity and suggests that the limited amount of SUMOylation normally observed for most SUMO targets may correspond to an optimal level that maximizes the contribution of SUMOylation to protein function. Finally, protein cross-linking data suggest that SUMOylation may affect NS1 function by regulating the abundance of NS1 dimers and trimers in the cell.

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“…Moreover, addition of both a consensus SUMO site and a NLS are necessary to confer SUMOylation upon an artificial substrate (Rodriguez et al 2001). SUMOylation is a reversible modification, and a family of SUMO-specific proteases has been identified that catalyze deSUMOylation (Smith et al 2004;Hay 2007).…”

mentioning

confidence: 99%

Medea SUMOylation restricts the signaling range of the Dpp morphogen in the Drosophila embryo

Miles¹,

Jaffray²,

Campbell³

et al. 2008

Genes Dev.

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Morphogens are secreted signaling molecules that form concentration gradients and control cell fate in developing tissues. During development, it is essential that morphogen range is strictly regulated in order for correct cell type specification to occur. One of the best characterized morphogens is Drosophila Decapentaplegic (Dpp), a BMP signaling molecule that patterns the dorsal ectoderm of the embryo by activating the Mad and Medea (Med) transcription factors. We demonstrate that there is a spatial and temporal expansion of the expression patterns of Dpp target genes in SUMO pathway mutant embryos. We identify Med as the primary SUMOylation target in the Dpp pathway, and show that failure to SUMOylate Med leads to the increased Dpp signaling range observed in the SUMO pathway mutant embryos. Med is SUMO modified in the nucleus, and we provide evidence that SUMOylation triggers Med nuclear export. Hence, Med SUMOylation provides a mechanism by which nuclei can continue to monitor the presence of extracellular Dpp signal to activate target gene expression for an appropriate duration. Overall, our results identify an unusual strategy for regulating morphogen range that, rather than impacting on the morphogen itself, targets an intracellular transducer. Med and its vertebrate ortholog Smad4 have been found to constitutively shuttle between the nucleus and cytoplasm in a signal-independent manner (Pierreux et al. 2000;Yao et al. 2008). Smad4 contains both a nuclear localization signal (NLS) and a CRM-1-dependent nuclear export signal (NES), and it has been proposed that the relative strengths of these two signals within a tissue regulate the amount of shuttling. Smad4, which shuttles into the nucleus in the absence of signal, is unable to activate transcription (Pierreux et al. 2000), possibly due to recruitment of a repressive complex harboring the SnoN oncoprotein (Stroschein et al. 1999).The small ubiquitin-like modifier protein SUMO is conjugated to its substrate through the sequential activities of E1, E2, and E3 enzymes. Ubc-9, the essential E2 enzyme, catalyzes the conjugation of SUMO to the target lysine, typically located in a ⌿KxE consensus motif (where ⌿ is a large hydrophobic residue and x is any residue) (Hay 2005). An extended SUMO motif compris-

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SUMO-specific proteases: a twist in the tail

Cited by 252 publications

References 69 publications

BCL11A is a SUMOylated protein and recruits SUMO‐conjugation enzymes in its nuclear body

BCL11A is a SUMOylated protein and recruits SUMO‐conjugation enzymes in its nuclear body

SUMOylation Affects the Interferon Blocking Activity of the Influenza A Nonstructural Protein NS1 without Affecting Its Stability or Cellular Localization

Medea SUMOylation restricts the signaling range of the Dpp morphogen in the Drosophila embryo

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