DSS1/Sem1, a Multifunctional and Intrinsically Disordered Protein

Kragelund, Birthe B.; Schenstrøm, Signe M.; Rebula, Caio A.; Panse, Vikram Govind; Hartmann‐Petersen, Rasmus

doi:10.1016/j.tibs.2016.02.004

Cited by 45 publications

(59 citation statements)

References 100 publications

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“…Rpn11 is a JAMM metalloprotease; Rpn8 is inactive but heterodimerizes with Rpn11, yielding a complex with modest DUB activity[130,131]. Sem1 (Rpn15) is a small intrinsically disordered protein that is also part of several other nonproteasomal protein complexes [132]. In the proteasome lid, Sem1 binds both Rpn3 and Rpn7[133–136].…”

Section: The Rp Lidmentioning

confidence: 99%

Proteasome Structure and Assembly

Budenholzer

Cheng

et al. 2017

Journal of Molecular Biology

304

280

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The eukaryotic 26S proteasome is a large multi-subunit complex that degrades the majority of proteins in the cell under normal conditions. The 26S proteasome can be divided into two subcomplexes: the 19S regulatory particle (RP) and the 20S core particle (CP). Most substrates are first covalently modified by ubiquitin, which then directs them to the proteasome. The function of the RP is to recognize, unfold, deubiquitylate and translocate substrates into the CP, which contains the proteolytic sites of the proteasome. Given the abundance and subunit complexity of the proteasome, the assembly of this ~2.5 MDa complex must be carefully orchestrated to ensure its correct formation. In recent years, significant advances have been made in the understanding of proteasome assembly, structure and function. Technical advances in cryo-electron microscopy have resulted in a series of atomic cryo-EM structures of both human and yeast 26S proteasomes. These structures have illuminated new intricacies and dynamics of the proteasome. In this review, we focus on the mechanisms of proteasome assembly, particularly in light of recent structural information.

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Section: The Rp Lidmentioning

confidence: 99%

Proteasome Structure and Assembly

Budenholzer

Cheng

et al. 2017

Journal of Molecular Biology

304

280

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“…(c) Regulating protein half-life by efficiently engaging proteins that have been targeted for degradation by the proteasome [53–59]. (d) Adopting different conformations when binding to different interaction partners [12,60–66]. These properties of IDRs make them well suited to perform signaling and regulatory functions.…”

Section: Advantages and Functions Mediated By Idrsmentioning

confidence: 99%

The contribution of intrinsically disordered regions to protein function, cellular complexity, and human disease

Babu

2016

Biochemical Society Transactions

330

294

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In the 1960s, Christian Anfinsen postulated that the unique three-dimensional structure of a protein is determined by its amino acid sequence. This work laid the foundation for the sequence–structure–function paradigm, which states that the sequence of a protein determines its structure, and structure determines function. However, a class of polypeptide segments called intrinsically disordered regions does not conform to this postulate. In this review, I will first describe established and emerging ideas about how disordered regions contribute to protein function. I will then discuss molecular principles by which regulatory mechanisms, such as alternative splicing and asymmetric localization of transcripts that encode disordered regions, can increase the functional versatility of proteins. Finally, I will discuss how disordered regions contribute to human disease and the emergence of cellular complexity during organismal evolution.

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“…1C). However, because Dss1/Sem1 is also linked to non-proteasomal functions (35), including transcription and mRNA maturation, this is likely to obscure a positive genetic interaction between dss1 and sec3 in S. pombe cells. However, as a further control, we also analyzed the growth of wild-type and sec3-913 cells on medium containing sublethal amounts of the proteasome inhibitor bortezomib (BZ).…”

Section: The Sec3-913 Protein Is a Proteasome Targetmentioning

confidence: 99%

The exocyst subunit Sec3 is regulated by a protein quality control pathway

Kampmeyer

Karakostova

Schenstrøm

et al. 2017

Journal of Biological Chemistry

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Exocytosis involves fusion of secretory vesicles with the plasma membrane, thereby delivering membrane proteins to the cell surface and releasing material into the extracellular space. The tethering of the secretory vesicles before membrane fusion is mediated by the exocyst, an essential phylogenetically conserved octameric protein complex. Exocyst biogenesis is regulated by several processes, but the mechanisms by which the exocyst is degraded are unknown. Here, to unravel the components of the exocyst degradation pathway, we screened for extragenic suppressors of a temperature-sensitive fission yeast strain mutated in the exocyst subunit Sec3 (). One of the suppressing DNAs encoded a truncated dominant-negative variant of the 26S proteasome subunit, Rpt2, indicating that exocyst degradation is controlled by the ubiquitin-proteasome system. The temperature-dependent growth defect of the strain was gene dosage-dependent and suppressed by blocking the proteasome, Hsp70-type molecular chaperones, the Pib1 E3 ubiquitin-protein ligase, and the deubiquitylating enzyme Ubp3. Moreover, defects in cell septation, exocytosis, and endocytosis in mutant strains were similarly alleviated by mutation of components in this pathway. We also found that, particularly under stress conditions, wild-type Sec3 degradation is regulated by Pib1 and the 26S proteasome. In conclusion, our results suggest that a cytosolic protein quality control pathway monitors folding and proteasome-dependent turnover of an exocyst subunit and, thereby, controls exocytosis in fission yeast.

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DSS1/Sem1, a Multifunctional and Intrinsically Disordered Protein

Cited by 45 publications

References 100 publications

Proteasome Structure and Assembly

Proteasome Structure and Assembly

The contribution of intrinsically disordered regions to protein function, cellular complexity, and human disease

The exocyst subunit Sec3 is regulated by a protein quality control pathway

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