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Intracellular Dynamics of the Ubiquitin-Proteasome-System.

Chowdhury M, Enenkel C - F1000Res (2015)

Bottom Line: Here, we summarize our knowledge about the enigmatic structure of proteasome storage granules and the trafficking of proteasomes and their substrates between the cyto- and nucleoplasm.Most of our current knowledge is based on studies in yeast.Their translation to mammalian cells promises to provide keen insight into protein degradation in non-dividing cells which comprise the majority of our body's cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Toronto, Toronto, ON, M5S 1A8, Canada.

ABSTRACT
The ubiquitin-proteasome system is the major degradation pathway for short-lived proteins in eukaryotic cells. Targets of the ubiquitin-proteasome-system are proteins regulating a broad range of cellular processes including cell cycle progression, gene expression, the quality control of proteostasis and the response to geno- and proteotoxic stress. Prior to degradation, the proteasomal substrate is marked with a poly-ubiquitin chain. The key protease of the ubiquitin system is the proteasome. In dividing cells, proteasomes exist as holo-enzymes composed of regulatory and core particles. The regulatory complex confers ubiquitin-recognition and ATP dependence on proteasomal protein degradation. The catalytic sites are located in the proteasome core particle. Proteasome holo-enzymes are predominantly nuclear suggesting a major requirement for proteasomal proteolysis in the nucleus. In cell cycle arrested mammalian or quiescent yeast cells, proteasomes deplete from the nucleus and accumulate in granules at the nuclear envelope (NE) / endoplasmic reticulum (ER) membranes. In prolonged quiescence, proteasome granules drop off the NE / ER membranes and migrate as stable organelles throughout the cytoplasm, as thoroughly investigated in yeast. When quiescence yeast cells are allowed to resume growth, proteasome granules clear and proteasomes are rapidly imported into the nucleus. Here, we summarize our knowledge about the enigmatic structure of proteasome storage granules and the trafficking of proteasomes and their substrates between the cyto- and nucleoplasm. Most of our current knowledge is based on studies in yeast. Their translation to mammalian cells promises to provide keen insight into protein degradation in non-dividing cells which comprise the majority of our body's cells.

No MeSH data available.


Related in: MedlinePlus

Nuclear import of RP base and lid subcomplexes by the classical importin/karyopherin αβ pathway.Rpn2/Rpt2 and Sts1 confer classical NLS to the RP base and lid complex, respectively. Sts1 is short-lived and most likely degraded with RP-CP assembly.
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f2: Nuclear import of RP base and lid subcomplexes by the classical importin/karyopherin αβ pathway.Rpn2/Rpt2 and Sts1 confer classical NLS to the RP base and lid complex, respectively. Sts1 is short-lived and most likely degraded with RP-CP assembly.

Mentions: In the case of the RP, functional NLSs were identified in RP base subunits Rpn2 and Rpt2 and are recognized by importin α (Figure 2). The deletion of the Rpn2 NLS caused a temperature sensitive phenotype and mislocalizations of the RP base into cytosolic foci, whereas the deletion of the Rpt2 NLS was compensated by the presence of the Rpn2 NLS. At permissive temperatures, neither the Rpn2 nor the Rpt2 NLS deletion had severe impact on nuclear proteasome localization suggesting a redundancy of proteasomal NLSs (Wendleret al., 2004).Isonoet al. (2007) later confirmed that Rpn2 provides a crucial NLS to aid nuclear import of the RP base and that the lid is separately imported. The nuclear import of the RP lid also requires importin α, though no classical NLS has been identified within RP lid subunits; rather Sts1, a short-lived protein that itself contains a classical NLS, associates with Rpn11 to facilitate nuclear import of the RP lid by importin αβ (Chenet al., 2011). In accordance, deletion of the Sts1 NLS has downstream effects on the nuclear localization of RP lid in addition to RP base and CP, which suggests that proteasomes could also be transported as holo-enzymes (Chen & Madura, 2014b). In order to ensure comparable stoichiometry of proteasomal subcomplexes in the nucleus and similar kinetics by which they are imported into the nucleus, it is reasonable that importin αβ is used as common nuclear import receptor.


Intracellular Dynamics of the Ubiquitin-Proteasome-System.

Chowdhury M, Enenkel C - F1000Res (2015)

Nuclear import of RP base and lid subcomplexes by the classical importin/karyopherin αβ pathway.Rpn2/Rpt2 and Sts1 confer classical NLS to the RP base and lid complex, respectively. Sts1 is short-lived and most likely degraded with RP-CP assembly.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4544378&req=5

f2: Nuclear import of RP base and lid subcomplexes by the classical importin/karyopherin αβ pathway.Rpn2/Rpt2 and Sts1 confer classical NLS to the RP base and lid complex, respectively. Sts1 is short-lived and most likely degraded with RP-CP assembly.
Mentions: In the case of the RP, functional NLSs were identified in RP base subunits Rpn2 and Rpt2 and are recognized by importin α (Figure 2). The deletion of the Rpn2 NLS caused a temperature sensitive phenotype and mislocalizations of the RP base into cytosolic foci, whereas the deletion of the Rpt2 NLS was compensated by the presence of the Rpn2 NLS. At permissive temperatures, neither the Rpn2 nor the Rpt2 NLS deletion had severe impact on nuclear proteasome localization suggesting a redundancy of proteasomal NLSs (Wendleret al., 2004).Isonoet al. (2007) later confirmed that Rpn2 provides a crucial NLS to aid nuclear import of the RP base and that the lid is separately imported. The nuclear import of the RP lid also requires importin α, though no classical NLS has been identified within RP lid subunits; rather Sts1, a short-lived protein that itself contains a classical NLS, associates with Rpn11 to facilitate nuclear import of the RP lid by importin αβ (Chenet al., 2011). In accordance, deletion of the Sts1 NLS has downstream effects on the nuclear localization of RP lid in addition to RP base and CP, which suggests that proteasomes could also be transported as holo-enzymes (Chen & Madura, 2014b). In order to ensure comparable stoichiometry of proteasomal subcomplexes in the nucleus and similar kinetics by which they are imported into the nucleus, it is reasonable that importin αβ is used as common nuclear import receptor.

Bottom Line: Here, we summarize our knowledge about the enigmatic structure of proteasome storage granules and the trafficking of proteasomes and their substrates between the cyto- and nucleoplasm.Most of our current knowledge is based on studies in yeast.Their translation to mammalian cells promises to provide keen insight into protein degradation in non-dividing cells which comprise the majority of our body's cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Toronto, Toronto, ON, M5S 1A8, Canada.

ABSTRACT
The ubiquitin-proteasome system is the major degradation pathway for short-lived proteins in eukaryotic cells. Targets of the ubiquitin-proteasome-system are proteins regulating a broad range of cellular processes including cell cycle progression, gene expression, the quality control of proteostasis and the response to geno- and proteotoxic stress. Prior to degradation, the proteasomal substrate is marked with a poly-ubiquitin chain. The key protease of the ubiquitin system is the proteasome. In dividing cells, proteasomes exist as holo-enzymes composed of regulatory and core particles. The regulatory complex confers ubiquitin-recognition and ATP dependence on proteasomal protein degradation. The catalytic sites are located in the proteasome core particle. Proteasome holo-enzymes are predominantly nuclear suggesting a major requirement for proteasomal proteolysis in the nucleus. In cell cycle arrested mammalian or quiescent yeast cells, proteasomes deplete from the nucleus and accumulate in granules at the nuclear envelope (NE) / endoplasmic reticulum (ER) membranes. In prolonged quiescence, proteasome granules drop off the NE / ER membranes and migrate as stable organelles throughout the cytoplasm, as thoroughly investigated in yeast. When quiescence yeast cells are allowed to resume growth, proteasome granules clear and proteasomes are rapidly imported into the nucleus. Here, we summarize our knowledge about the enigmatic structure of proteasome storage granules and the trafficking of proteasomes and their substrates between the cyto- and nucleoplasm. Most of our current knowledge is based on studies in yeast. Their translation to mammalian cells promises to provide keen insight into protein degradation in non-dividing cells which comprise the majority of our body's cells.

No MeSH data available.


Related in: MedlinePlus