SUMO-targeted ubiquitin ligase (STUbL) Slx5 regulates proteolysis of centromeric histone H3 variant Cse4 and prevents its mislocalization to euchromatin

Ohkuni, Kentaro; Takahashi, Yoshimitsu; Fulp, Alyona; Lawrimore, Josh; Au, Wei Chun; Pasupala, Nagesh; Levy-Myers, Reuben; Warren, Jack; Strunnikov, Alexander; Baker, Richard E.; Kerscher, Oliver; Bloom, Kerry; Basrai, Munira A.

doi:10.1091/mbc.e15-12-0827

Cited by 69 publications

(94 citation statements)

References 59 publications

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“…So far, four E3 ubiquitin ligases have been reported to mediate CENP-A Cse4 ubiquitylation. These include Psh1, Rcy1, Slx5 and Ubr1 [17–19,20 • ,21 • ,22,23]. CENP-A Cse4 is protected from degradation at the centromere, while CENP-A Cse4 in chromosome arms is degraded.…”

Section: Intrinsic Features Of Cenp-a Modifications and Ccan Recruitmentmentioning

confidence: 99%

“…CENP-A Cse4 is protected from degradation at the centromere, while CENP-A Cse4 in chromosome arms is degraded. Notably, Slx5 mediated ubiquitylation is dependent on SUMOylation of CENP-A Cse4 [21 • ], suggesting that CENP-A Cse4 degradation may be under complex regulatory control. Drosophila dCENP-A CID protein levels are regulated by the F-Box Protein Partner of Paired (Ppa), a component of the SCF E3-ubiquitin ligase complex [24].…”

Section: Intrinsic Features Of Cenp-a Modifications and Ccan Recruitmentmentioning

confidence: 99%

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Posttranslational mechanisms controlling centromere function and assembly

Srivastava

Zasadzińska

Foltz

2018

Current Opinion in Cell Biology

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Accurate chromosome segregation is critical to ensure the faithful inheritance of the genome during cell division. Human chromosomes distinguish the location of the centromere from general chromatin by the selective assembly of CENP-A containing nucleosomes at the active centromere. The location of centromeres in most higher eukaryotes is determined epigenetically, independent of DNA sequence. CENP-A containing centromeric chromatin provides the foundation for assembly of the kinetochore that mediates chromosome attachment to the microtubule spindle and controls cell cycle progression in mitosis. Here we review recent work demonstrating the role of posttranslational modifications on centromere function and CENP-A inheritance via the direct modification of the CENP-A nucleosome and pre-nucleosomal complexes, the modification of the CENP-A deposition machinery and the modification of histones within existing centromeres.

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Section: Intrinsic Features Of Cenp-a Modifications and Ccan Recruitmentmentioning

confidence: 99%

Section: Intrinsic Features Of Cenp-a Modifications and Ccan Recruitmentmentioning

confidence: 99%

Posttranslational mechanisms controlling centromere function and assembly

Srivastava

Zasadzińska

Foltz

2018

Current Opinion in Cell Biology

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“…Ubiquitylation has been reported to prevent the ectopic localization of Cse4 by triggering its degradation, and the E3 ubiquitin ligases Psh1, Rcy1, Slx5, and Ubr1 have been shown to ubiquitylate Cse4 (Fig. 5) (Au et al 2013; Cheng et al 2017; Cheng et al 2016; Collins et al 2004; Hewawasam et al 2010; Ohkuni et al 2016; Ranjitkar et al 2010). While Psh1 ubiquitylates Lys-4, Lys-131, Lys-155, Lys-163 and Lys-172 (Hewawasam et al 2010), Slx5-mediated proteolysis of Cse4 is directed by sumoylation at Lys-65 (Ohkuni et al 2018) (Fig.…”

Section: Diversity Of Cenp-a Modifications Across Speciesmentioning

confidence: 99%

“…The SUMO E3 ligases Siz1 and Siz2 target Cse4 for sumoylation, which further undergoes ubiquitylation by the ubiquitin ligase Slx5 (Fig. 5) (Ohkuni et al 2016). …”

Section: Diversity Of Cenp-a Modifications Across Speciesmentioning

confidence: 99%

Posttranslational modifications of CENP-A: marks of distinction

Srivastava

Foltz

2018

Chromosoma

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Centromeres are specialized chromosome domain that serve as the site for kinetochore assembly and microtubule attachment during cell division, to ensure proper segregation of chromosomes. In higher eukaryotes, the identity of active centromeres is marked by the presence of CENP-A (centromeric protein-A), a histone H3 variant. CENP-A forms a centromere-specific nucleosome that acts as a foundation for centromere assembly and function. The posttranslational modification (PTM) of histone proteins is a major mechanism regulating the function of chromatin. While a few CENP-A site-specific modifications are shared with histone H3, the majority are specific to CENP-A-containing nucleosomes, indicating that modification of these residues contribute to centromere-specific function. CENP-A undergoes posttranslational modifications including phosphorylation, acetylation, methylation, and ubiquitylation. Work from many laboratories have uncovered the importance of these CENP-A modifications in its deposition at centromeres, protein stability, and recruitment of the CCAN (constitutive centromere-associated network). Here, we discuss the PTMs of CENP-A and their biological relevance.

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“…Slx5/Slx8 is involved in the repositioning of DNA lesions to nuclear pore complexes (Nagai et al, 2008;Su et al, 2015;Churikov et al, 2016;Horigome et al, 2016). In line with an additional major function in chromatin maintenance, several DNA-associated proteins have been described as Slx5/Slx8 substrates (Ohkuni et al, 2016;Schweiggert et al, 2016;Thu et al, 2016;Liang et al, 2017), including transcription factors (TFs) such as Mot1 (mutant variant) and Mata2 (Wang & Prelich, 2009;Xie et al, 2010). Interestingly, in the latter case, Mata2 SUMOylation is dispensable for Slx5/Slx8 targeting, but the SIMs of Slx5 and Mata2 DNA binding are required (Xie et al, 2010;Hickey et al, 2018).…”

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confidence: 99%

Slx5/Slx8‐dependent ubiquitin hotspots on chromatin contribute to stress tolerance

et al. 2019

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Chromatin is a highly regulated environment, and protein association with chromatin is often controlled by post‐translational modifications and the corresponding enzymatic machinery. Specifically, SUMO ‐targeted ubiquitin ligases ( STU bLs) have emerged as key players in nuclear quality control, genome maintenance, and transcription. However, how STU bLs select specific substrates among myriads of SUMO ylated proteins on chromatin remains unclear. Here, we reveal a remarkable co‐localization of the budding yeast STU bL Slx5/Slx8 and ubiquitin at seven genomic loci that we term “ubiquitin hotspots”. Ubiquitylation at these sites depends on Slx5/Slx8 and protein turnover on the Cdc48 segregase. We identify the transcription factor‐like Ymr111c/Euc1 to associate with these sites and to be a critical determinant of ubiquitylation. Euc1 specifically targets Slx5/Slx8 to ubiquitin hotspots via bipartite binding of Slx5 that involves the Slx5 SUMO ‐interacting motifs and an additional, novel substrate recognition domain. Interestingly, the Euc1‐ubiquitin hotspot pathway acts redundantly with chromatin modifiers of the H2A.Z and Rpd3L pathways in specific stress responses. Thus, our data suggest that STU bL‐dependent ubiquitin hotspots shape chromatin during stress adaptation.

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SUMO-targeted ubiquitin ligase (STUbL) Slx5 regulates proteolysis of centromeric histone H3 variant Cse4 and prevents its mislocalization to euchromatin

Cited by 69 publications

References 59 publications

Posttranslational mechanisms controlling centromere function and assembly

Posttranslational mechanisms controlling centromere function and assembly

Posttranslational modifications of CENP-A: marks of distinction

Slx5/Slx8‐dependent ubiquitin hotspots on chromatin contribute to stress tolerance

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