Regulated nuclear accumulation of the yeast hsp70 Ssa4p in ethanol‐stressed cells is mediated by the N‐terminal domain, requires the nuclear carrier Nmd5p and protein kinase C

Quan, XinXin; Rassadi, Roozbeh; Rabie, Bashir; Matusiewicz, Neola; Stochaj, Ursula

doi:10.1096/fj.03-0947fje

Cited by 23 publications

(35 citation statements)

References 49 publications

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“…However, yeast Hsf1 is largely trimerized, nuclear, and DNA bound in unstressed cells (McDaniel et al 1989;; therefore, the chaperone repression model has to be revised: protein misfolding (in the nucleus) must be sensed by nuclear chaperones or cytoplasmic misfolding events must titrate chaperones that transit between the two compartments, depleting the nuclear pool. In support of this latter argument, both Hsp70 (Ssa4) and Hsp90 (Hsp82 and Hsc82) can localize to the nucleus in response to environmental stress (Chughtai et al 2001;Quan et al 2004;Tapia and Morano 2010).…”

Section: Control and Regulation Of The Heat Shock Responsementioning

confidence: 84%

The Response to Heat Shock and Oxidative Stress inSaccharomyces cerevisiae

2012

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A common need for microbial cells is the ability to respond to potentially toxic environmental insults. Here we review the progress in understanding the response of the yeast Saccharomyces cerevisiae to two important environmental stresses: heat shock and oxidative stress. Both of these stresses are fundamental challenges that microbes of all types will experience. The study of these environmental stress responses in S. cerevisiae has illuminated many of the features now viewed as central to our understanding of eukaryotic cell biology. Transcriptional activation plays an important role in driving the multifaceted reaction to elevated temperature and levels of reactive oxygen species. Advances provided by the development of whole genome analyses have led to an appreciation of the global reorganization of gene expression and its integration between different stress regimens. While the precise nature of the signal eliciting the heat shock response remains elusive, recent progress in the understanding of induction of the oxidative stress response is summarized here. Although these stress conditions represent ancient challenges to S. cerevisiae and other microbes, much remains to be learned about the mechanisms dedicated to dealing with these environmental parameters.

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Section: Control and Regulation Of The Heat Shock Responsementioning

confidence: 84%

The Response to Heat Shock and Oxidative Stress inSaccharomyces cerevisiae

2012

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“…No defects in alcohol-mediated nucleolar targeting were observed in any of these strains. Finally, we characterized Ulp1 nucleolar targeting in yeast strains lacking proteins previously reported to be recruited to the nucleus in response to alcohol treatment, i.e., Asr1 (2), Nmd5, and Ssa4 (24). Ulp1 was efficiently recruited to the nucleolus in an alcohol-dependent manner in all of these strains (Sydorskyy et al, unpublished).…”

Section: Discussionmentioning

confidence: 96%

A Novel Mechanism for SUMO System Control: Regulated Ulp1 Nucleolar Sequestration

Sydorskyy

Srikumar

Jeram

et al. 2010

Molecular and Cellular Biology

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The small ubiquitin-related modifiers (SUMOs) are evolutionarily conserved polypeptides that are covalently conjugated to protein targets to modulate their subcellular localization, half-life, or activity. Steadystate SUMO conjugation levels increase in response to many different types of environmental stresses, but how the SUMO system is regulated in response to these insults is not well understood. Here, we characterize a novel mode of SUMO system control: in response to elevated alcohol levels, the Saccharomyces cerevisiae SUMO protease Ulp1 is disengaged from its usual location at the nuclear pore complex (NPC) and sequestered in the nucleolus. We further show that the Ulp1 region previously demonstrated to interact with the karyopherins Kap95 and Kap60 (amino acids 150 to 340) is necessary and sufficient for nucleolar targeting and that enforced sequestration of Ulp1 in the nucleolus significantly increases steady-state SUMO conjugate levels, even in the absence of alcohol. We have thus characterized a novel mechanism of SUMO system control in which the balance between SUMO-conjugating and -deconjugating activities at the NPC is altered in response to stress via relocalization of a SUMO-deconjugating enzyme.The small ubiquitin-related modifiers (SUMOs) are a family of evolutionarily conserved polypeptides that are conjugated to protein targets via the concerted action of SUMO-specific E1 (activation), E2 (conjugation), and E3 (ligase) enzymes to effect changes in subcellular localization, half-life, or target activity. A family of SUMO-specific proteases act to remove the modifier from conjugates (8,20). The SUMO system has been implicated in a variety of critical cellular functions, such as DNA repair and replication, RNA metabolism, and stress responses (8,16,20). Importantly, the SUMO system is highly dynamic and the SUMO pathway enzymes appear to work together to precisely control SUMO conjugate levels in the cell (8,16,20). However, how the SUMO system itself is regulated is poorly understood.Localization of the SUMO pathway enzymes may play an important role in SUMO system function (21). For example, the budding yeast SUMO protease Ulp1 is tethered to the nuclear face of the nuclear pore complex (NPC) via an unconventional interaction with the karyopherin Kap121 and the heterodimeric Kap95/Kap60 complex (12, 13, 23). However, this SUMO protease is not maintained exclusively at the NPC but appears to be mobile, effecting desumoylation at diverse subcellular locations: e.g., during mitosis, Saccharomyces cerevisiae Ulp1 is recruited to the septin ring to desumoylate septins (15), Schizosaccharomyces pombe Ulp1 localization is regulated throughout the cell cycle (31), and a mammalian Ulp1 homolog, SENP2, is shuttled between the nucleus and the cytoplasm (7). Consistent with these observations, SUMO conjugate levels are significantly altered in yeast strains expressing mislocalized Ulp1 (13, 37).Dramatic changes in SUMO conjugate populations have been noted in response to many different types of stresses ...

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“…Evidence that a nuclear UPR might exist comes from the increased expression of nuclear chaperone and stress response genes when the San1 function is compromised [10]. Particular chaperone genes include those that encode for Ssa4, Hsp26, and Hsp104, all of which become enriched in the nucleus upon exposure of cells to protein misfolding stressors [70–72,74,108–110]. Revealing how nuclear PQC systems are coordinately regulated to protect the nuclear environment will be essential to understanding how these systems might fail during aging and lead to nuclear aggregation diseases.…”

Section: Discussionmentioning

confidence: 99%

Protein quality control in the nucleus

Jones

Gardner

2016

Current Opinion in Cell Biology

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The nucleus is the repository for the eukaryotic cell’s genetic blueprint, which must be protected from harm to ensure survival. Multiple quality control (QC) pathways operate in the nucleus to maintain the integrity of the DNA, the fidelity of the DNA code during replication, its transcription into mRNA, and the functional structure of the proteins that are required for DNA maintenance, mRNA transcription, and other important nuclear processes. Although we understand a great deal about DNA and RNA QC mechanisms, we know far less about nuclear protein quality control (PQC) mechanisms despite that fact that many human diseases are causally linked to protein misfolding in the nucleus. In this review, we discuss what is known about nuclear PQC and we highlight new questions that have emerged from recent developments in nuclear PQC studies.

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Regulated nuclear accumulation of the yeast hsp70 Ssa4p in ethanol‐stressed cells is mediated by the N‐terminal domain, requires the nuclear carrier Nmd5p and protein kinase C

Cited by 23 publications

References 49 publications

The Response to Heat Shock and Oxidative Stress inSaccharomyces cerevisiae

The Response to Heat Shock and Oxidative Stress inSaccharomyces cerevisiae

A Novel Mechanism for SUMO System Control: Regulated Ulp1 Nucleolar Sequestration

Protein quality control in the nucleus

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