Binding to small ubiquitin-like modifier and the nucleolar protein Csm1 regulates substrate specificity of the Ulp2 protease.

de Albuquerque, Claudio Ponte; Suhandynata, Raymond T; Carlson, Christopher R; Yuan, Wei-Tsung; Zhou, Huilin

de Albuquerque, Claudio Ponte; Suhandynata, Raymond T; Carlson, Christopher R; Yuan, Wei-Tsung; Zhou, Huilin.

Afiliación

de Albuquerque CP; Ludwig Institute for Cancer Research, San Diego Branch, University of California, San Diego, La Jolla, California 92093.
Suhandynata RT; Ludwig Institute for Cancer Research, San Diego Branch, University of California, San Diego, La Jolla, California 92093.
Carlson CR; Ludwig Institute for Cancer Research, San Diego Branch, University of California, San Diego, La Jolla, California 92093.
Yuan WT; Ludwig Institute for Cancer Research, San Diego Branch, University of California, San Diego, La Jolla, California 92093; Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093.
Zhou H; Ludwig Institute for Cancer Research, San Diego Branch, University of California, San Diego, La Jolla, California 92093; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093; Moores Cancer Center, University of California, San Diego, La Jolla

J Biol Chem ; 293(31): 12105-12119, 2018 08 03.

Article en En | MEDLINE | ID: mdl-29903909

RESUMEN

Ulp1 and Ulp2, in the yeast Saccharomyces cerevisiae, are the founding members of deSUMOylating enzymes. These enzymes remove small ubiquitin-like modifier (SUMO) from proteins and are conserved in all eukaryotes. Previous studies have shown that Ulp1 deSUMOylates the bulk of intracellular SUMOylated proteins, whereas Ulp2 is a highly specific enzyme. However, the mechanism for Ulp2's substrate specificity has been insufficiently understood. Here we show that the C-terminal regulatory domain of Ulp2 contains three distinct, yet conserved, motifs that control its in vivo substrate specificity and cell growth. Among them, a SUMO-interacting motif (SIM) was found to coordinate with the domain of Ulp2 that binds to the nucleolar protein Csm1 to ensure maximal deSUMOylation of Ulp2's nucleolar substrates. We found that whereas the Csm1-binding domain of Ulp2 recruits this enzyme to the nucleolus, Ulp2's C-terminal SIM promotes its SUMO protease activity and plays a key role in mediating the in vivo specificity of Ulp2. Thus, the substrate specificity of Ulp2 is controlled by both its subcellular localization and the SUMOylation status of its substrates. These findings illustrate the highly coordinated and dynamic nature of the SUMO pathways in maintaining homeostasis of intracellular SUMOylation.

Asunto(s)

Proteínas de Ciclo Celular/metabolismo; Núcleo Celular/metabolismo; Endopeptidasas/química; Proteínas Nucleares/metabolismo; Procesamiento Proteico-Postraduccional; Proteínas de Saccharomyces cerevisiae/química; Proteínas de Saccharomyces cerevisiae/metabolismo; Saccharomyces cerevisiae/metabolismo; Ubiquitina/metabolismo; Secuencia de Aminoácidos; Sitios de Unión; Proteínas de Ciclo Celular/genética; Núcleo Celular/genética; Cisteína Endopeptidasas/genética; Cisteína Endopeptidasas/metabolismo; Endopeptidasas/genética; Endopeptidasas/metabolismo; Regulación Fúngica de la Expresión Génica; Cinética; Proteínas Nucleares/genética; Unión Proteica; Dominios y Motivos de Interacción de Proteínas; Saccharomyces cerevisiae/genética; Proteínas de Saccharomyces cerevisiae/genética; Alineación de Secuencia; Homología de Secuencia de Aminoácido; Transducción de Señal; Especificidad por Sustrato; Sumoilación; Ubiquitina/genética; Ubiquitinación

Palabras clave

Cdc14; Net1; SUMO-interacting motif (SIM); Tof2; Ulp1; Ulp2; isothermal titration calorimetry (ITC); post-translational modification (PTM); protease; substrate specificity; sumoylation

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Endopeptidasas / Saccharomyces cerevisiae / Proteínas Nucleares / Núcleo Celular / Procesamiento Proteico-Postraduccional / Proteínas de Ciclo Celular / Proteínas de Saccharomyces cerevisiae / Ubiquitina Idioma: En Revista: J Biol Chem Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos

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