Phospho-Regulated SUMO Interaction Modules Connect the SUMO System to CK2 Signaling

Stehmeier, Per; Müller, Stefan

doi:10.1016/j.molcel.2009.01.013

Cited by 136 publications

(151 citation statements)

References 52 publications

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“…A SIM facilitate interactions with SUMO isoforms or SUMO-conjugated proteins (reviewed in references 34 and 36). A recent publication showed that phosphorylation of SIM domains in at least three cellular proteins, including PML, significantly enhances their interaction with SUMO isoforms (62). Thus, in the case of Phos 2, blocking phosphorylation in region II may impede this putative SUMO-binding activity, affecting its interaction with SUMO-conjugated proteins (such as PML) or specific SUMO isoforms.…”

Section: Discussionmentioning

confidence: 99%

Herpes Simplex Virus 1 ICP0 Phosphorylation Site Mutants Are Attenuated for Viral Replication and Impaired for Explant-Induced Reactivation

Mostafa

Thompson

Kushnir

et al. 2011

J Virol

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Section: Discussionmentioning

confidence: 99%

Herpes Simplex Virus 1 ICP0 Phosphorylation Site Mutants Are Attenuated for Viral Replication and Impaired for Explant-Induced Reactivation

Mostafa

Thompson

Kushnir

et al. 2011

J Virol

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“…GST fusion proteins were expressed in Escherichia coli BL21 as described previously (23). For in vitro transcription/translation, the TnT quick coupled transcription/translation system from Promega was used.…”

Section: Methodsmentioning

confidence: 99%

mTOR Signaling Regulates Nucleolar Targeting of the SUMO-Specific Isopeptidase SENP3

Raman

Nayak

2014

Molecular and Cellular Biology

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Ribosome biogenesis is a multistep cellular pathway that involves more than 200 regulatory components to ultimately generate translation-competent 80S ribosomes. The initial steps of this process, particularly rRNA processing, take place in the nucleolus, while later stages occur in the nucleoplasm and cytoplasm. One critical factor of 28S rRNA maturation is the SUMO-isopeptidase SENP3. SENP3 tightly interacts with the nucleolar scaffold protein NPM1 and is associated with nucleolar 60S preribosomes. A central question is how changes in energy supply feed into the regulation of ribosome maturation. Here, we show that the nutrient-sensing mTOR kinase pathway controls the nucleolar targeting of SENP3 by regulating its interaction with NPM1. We define an N-terminal domain in SENP3 as the critical NPM1 binding region and provide evidence that mTOR-mediated phosphorylation of serine/threonine residues within this region fosters the interaction of SENP3 with NPM1. The inhibition of mTOR triggers the nucleolar release of SENP3, thereby likely compromising its activity in rRNA processing. Since mTOR activity is tightly coupled to nutrient availability, we propose that this pathway contributes to the adaptation of ribosome maturation in response to the cellular energy status. Ribosomes are large ribonucleoprotein complexes functioning as molecular machines in protein synthesis. Mammalian 80S ribosomes are assembled from the small 40S and the large 60S subunit (1). The 60S subunit is composed of the 28S, the 5.8S, and the 5S rRNA and contains at least 46 ribosomal proteins, while the 40S subunit consists of around 30 ribosomal proteins and the 18S rRNA. The maturation of ribosomes is a highly regulated pathway that involves more than 200 nonribosomal proteins, commonly termed trans-acting factors (2, 3). Ribosome biogenesis is initiated in the nucleolus by RNA polymerase I (Pol I), transcribing a 47S precursor rRNA. This precursor is incorporated into a nucleolar 90S preribosomal particle, where specific bases in the rRNA are covalently modified and initial pre-RNA processing steps take place (4, 5). The 40S and 60S ribosomal subunits subsequently take a separate maturation pathway, which proceeds by a number of processing and remodelling events in the nucleolus and the nucleoplasm. Following export to the cytoplasm, both subunits are assembled to translation-competent 80S particles.As an integral part of protein synthesis, ribosome biogenesis must be tightly coupled to the energy status and nutrient levels of the cell. One key pathway that coordinates energy supply with protein translation is the mammalian target of rapamycin (mTOR) signaling network (6, 7). mTOR is an evolutionarily conserved serine/threonine kinase. In mammalian cells, mTOR is found in two distinct complexes, mTORC1 and mTORC2, that contain specific regulatory subunits and adaptor proteins. For example, Raptor and Rictor are the protein components involved in substrate recruitment and complex assembly of mTORC1 and mTORC2, respectively. mTORC1 positive...

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“…These have been shown to engage in electrostatic interaction with basic residues in the N-terminal extension and the Ubl domain of LC3 (R10, R11, K49 and K50) (Pankiv et al, 2007;Rogov et al, 2013;Shvets et al, 2008). It is worth noting that phospho-regulation of the LIR-LC3 interaction is reminiscent of that between small ubiquitin-related modifier (SUMO) and the SUMO-interacting motif (SIM) (Chang et al, 2011a;Hecker et al, 2006;Stehmeier and Muller, 2009). One atypical LIR motif regulates the interaction of the autophagy receptor NDP52 (also known as CALCOCO2) with LC3C.…”

Section: Characteristics Of the Lc3-interacting Regionmentioning

confidence: 99%

The LC3 interactome at a glance

Wild

McEwan

Đikić

2014

Journal of Cell Science

239

240

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Continuous synthesis of all cellular components requires their constant turnover in order for a cell to achieve homeostasis. To this end, eukaryotic cells are endowed with two degradation pathways -the ubiquitinproteasome system and the lysosomal pathway. The latter pathway is partly fed by autophagy, which targets intracellular material in distinct vesicles, termed autophagosomes, to the lysosome. Central to this pathway is a set of key autophagy proteins, including the ubiquitin-like modifier Atg8, that orchestrate autophagosome initiation and biogenesis. In higher eukaryotes, the Atg8 family comprises six members known as the light chain 3 (LC3) or c-aminobutyric acid (GABA)-receptorassociated protein (GABARAP) proteins. Considerable effort during the last 15 years to decipher the molecular mechanisms that govern autophagy has significantly advanced our understanding of the functioning of this protein family. In this Cell Science at a Glance article and the accompanying poster, we present the current LC3 protein interaction network, which has been and continues to be vital for gaining insight into the regulation of autophagy.

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Phospho-Regulated SUMO Interaction Modules Connect the SUMO System to CK2 Signaling

Cited by 136 publications

References 52 publications

Herpes Simplex Virus 1 ICP0 Phosphorylation Site Mutants Are Attenuated for Viral Replication and Impaired for Explant-Induced Reactivation

Herpes Simplex Virus 1 ICP0 Phosphorylation Site Mutants Are Attenuated for Viral Replication and Impaired for Explant-Induced Reactivation

mTOR Signaling Regulates Nucleolar Targeting of the SUMO-Specific Isopeptidase SENP3

The LC3 interactome at a glance

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