SUMO-specific proteases and isopeptidases of the SENP family at a glance

Kunz, Kathrin; Piller, Tanja; Müller, Stefan

doi:10.1242/jcs.211904

Cited by 207 publications

(168 citation statements)

References 99 publications

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“…SUMO proteins are highly conserved through evolution and the human genome encodes four SUMO genes, of which three genes (SUMO1, SUMO2, and SUMO3) are ubiquitously expressed in all cells 1,2 . Prior to conjugation, the immature SUMO proteins are C-terminally processed by sentrin-specific proteases 3 . These proteases also cleave the isopeptide bond formed between the ε-amino group of the acceptor lysine residues and the C-terminus residue of the conjugated SUMO proteins.…”

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confidence: 99%

Quantitative SUMO proteomics identifies PIAS1 substrates involved in cell migration and motility

McManus

Plutoni

et al. 2020

Nat Commun

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The protein inhibitor of activated STAT1 (PIAS1) is an E3 SUMO ligase that plays important roles in various cellular pathways. Increasing evidence shows that PIAS1 is overexpressed in various human malignancies, including prostate and lung cancers. Here we used quantitative SUMO proteomics to identify potential substrates of PIAS1 in a system-wide manner. We identified 983 SUMO sites on 544 proteins, of which 62 proteins were assigned as putative PIAS1 substrates. In particular, vimentin (VIM), a type III intermediate filament protein involved in cytoskeleton organization and cell motility, was SUMOylated by PIAS1 at Lys-439 and Lys-445 residues. VIM SUMOylation was necessary for its dynamic disassembly and cells expressing a non-SUMOylatable VIM mutant showed a reduced level of migration. Our approach not only enables the identification of E3 SUMO ligase substrates but also yields valuable biological insights into the unsuspected role of PIAS1 and VIM SUMOylation on cell motility.

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confidence: 99%

Quantitative SUMO proteomics identifies PIAS1 substrates involved in cell migration and motility

McManus

Plutoni

et al. 2020

Nat Commun

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“…The ability of Exendin 4 and DPPIV inhibitor to increase insulin secretion (and improve glucose tolerance) appears to depend on the expression of SENP1 within β‐cells, as indicated both by the inability of Exendin 4 to enhance β‐cell exocytosis in the βSENP1 −/− cells and the inability of the MK‐0626 DPPIV inhibitor to increase plasma insulin acutely and improve glucose tolerance in either the βSENP1 +/− or the βSENP1 − / − mice. SENP1 is an isopeptidase that selectively cleaves SUMO peptides from their target proteins (Kunz, Piller, and Müller, 2018). SENP1 is redox‐sensitive (Xu et al, 2008) and within β‐cells appears to be activated downstream of the glucose‐induced mitochondrial export of (iso)citrate (Ferdaoussi et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Improved glucose tolerance with DPPIV inhibition requires β‐cell SENP1 amplification of glucose‐stimulated insulin secretion

et al. 2020

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Pancreatic islet insulin secretion is amplified by both metabolic and receptor-mediated signaling pathways. The incretin-mimetic and DPPIV inhibitor anti-diabetic drugs increase insulin secretion, but in humans this can be variable both in vitro and in vivo. We examined the correlation of GLP-1 induced insulin secretion from human islets with key donor characteristics, glucose-responsiveness, and the ability of glucose to augment exocytosis in β-cells. No clear correlation was observed between several donor or organ processing parameters and the ability of Exendin 4 to enhance insulin secretion. The ability of glucose to facilitate β-cell exocytosis was, however, significantly correlated with responses to Exendin 4. We therefore studied the effect of impaired glucose-dependent amplification of insulin exocytosis on responses to DPPIV inhibition (MK-0626) in vivo using pancreas and β-cell specific sentrin-specific protease-1 (SENP1) mice which exhibit impaired metabolic amplification of insulin exocytosis. Glucose tolerance was improved, and plasma insulin was increased, following either acute or 4 week treatment of wild-type (βSENP1 +/+ ) mice with MK-0626. This DPPIV inhibitor was ineffective in βSENP1 +/− or βSENP1 −/− mice. Finally, we confirm impaired exocytotic responses of β-cells and reduced insulin secretion from islets of βSENP1 −/− mice and show that the ability of Exendin 4 to enhance exocytosis is lost in these cells. Thus, an impaired ability of glucose to amplify insulin exocytosis results in a deficient effect of DPPIV inhibition to improve in vivo insulin responses and glucose tolerance.

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“…In addition, SENPs display SUMO paralog specificity and thus serve as critical determinants of SUMO pathways. Detailed review on SENPs can be found elsewhere [68,69,70].…”

Section: The Sumo Pathway and The Cellular Sumo Landscapementioning

confidence: 99%

SUMO system – a key regulator in sarcomere organization

Nayak

Amrute-Nayak

2020

The FEBS Journal

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Skeletal muscles constitute roughly 40% of human body mass. Muscles are specialized tissues that generate force to drive movements through ATP-driven cyclic interactions between the protein filaments, namely actin and myosin filaments. The filaments are organized in an intricate structure called the 'sarcomere', which is a fundamental contractile unit of striated skeletal and cardiac muscle, hosting a fine assembly of macromolecular protein complexes. The micrometer-sized sarcomere units are arranged in a reiterated array within myofibrils of muscle cells. The precise spatial organization of sarcomere is tightly controlled by several molecular mechanisms, indispensable for its force-generating function. Disorganized sarcomeres, either due to erroneous molecular signaling or due to mutations in the sarcomeric proteins, lead to human diseases such as cardiomyopathies and muscle atrophic conditions prevalent in cachexia. Protein post-translational modifications (PTMs) of the sarcomeric proteins serve a critical role in sarcomere formation (sarcomerogenesis), as well as in the steady-state maintenance of sarcomeres. PTMs such as phosphorylation, acetylation, ubiquitination, and SUMOylation provide cells with a swift and reversible means to adapt to an altered molecular and therefore cellular environment. Over the past years, SUMOylation has emerged as a crucial modification with implications for different aspects of cell function, including organizing higher-order protein assemblies. In this review, we highlight the fundamentals of the small ubiquitin-like modifiers (SUMO) pathway and its link specifically to the mechanisms of sarcomere assembly. Furthermore, we discuss recent studies connecting the SUMO pathway-modulated protein homeostasis with sarcomere organization and muscle-related pathologies.Abbreviations ASH2L, ASH2 Like, Histone Lysine Methyltransferase Complex Subunit; CapZ, F-actin capping protein; Ckm, creatine kinase M-type; cMyBP-C, cardiac myosin binding protein C; Ezh2, enhancer of zeste homolog 2; G9a, euchromatin histone methyltransferase 2; H3K27me3, trimethylation of lysine 27 on histone 3; HDAC, histone deacetylase; hMR-1, human myofibrillogenesis regulator 1; IFN, interferon; Suv39h1, suppressor of variegation 3-9 homolog 1; IjBa, inhibitor of kappa B; Mck, muscle creatine kinase; MEF2d, myocyte enhancer factor-2d; MLCK, myosin light chain kinase; MLL, mixed-lineage leukemia; MLP, muscle LIM protein; MRFs, the myogenic regulatory factors; Myf5, Myc-like basic helix-loop-helix transcription factor; MyHC IIb or Myh2, myosin heavy chain II; MyoD, myoblast determination factor; MYOG, myogenin; NMM II, nonmuscle myosin II; Nse2, non-structural maintenance of chromosome element 2 homolog; Pax7, paired-box 7; PCAF, p300/CBP-associated factor; PcG proteins, polycomb-group proteins; PRC, polycomb repressive complexes; PTMs, post-translational modifications; RLC, regulatory light chains; RNA Pol II, RNA polymerase II; ROS, reactive oxygen species; SAE 1/2, SUMO-activating enzyme 1 or 2; SAE1/2, SUMO E1-a...

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SUMO-specific proteases and isopeptidases of the SENP family at a glance

Cited by 207 publications

References 99 publications

Quantitative SUMO proteomics identifies PIAS1 substrates involved in cell migration and motility

Quantitative SUMO proteomics identifies PIAS1 substrates involved in cell migration and motility

Improved glucose tolerance with DPPIV inhibition requires β‐cell SENP1 amplification of glucose‐stimulated insulin secretion

SUMO system – a key regulator in sarcomere organization

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