The spindle and kinetochore–associated (Ska) complex enhances binding of the anaphase-promoting complex/cyclosome (APC/C) to chromosomes and promotes mitotic exit

Sivakumar, Sushama; Daum, John R.; Tipton, Aaron R.; Rankin, Susannah; Gorbsky, Gary J.

doi:10.1091/mbc.e13-07-0421

Cited by 67 publications

(101 citation statements)

References 46 publications

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“…Modification of Ser92 in Cdc20 prevents binding to Ube2S, but not the MCC or APC/C, thereby blocking the formation of a complex important for the recruitment of Ube2S to the APC/C. Accordingly, phosphorylation impairs the ability of the APC/C to activate Ube2S, which could provide a basis for previous observations that hypophosphorylated APC/C displays higher activity than the heavily phosphorylated APC/C present in early mitotic cells (46). Ser92 of Cdc20 is modified by a kinetochore-bound complex composed of a Bub1 scaffold and Plk1 kinase (47).…”

Section: Discussionmentioning

confidence: 71%

Control of APC/C-dependent ubiquitin chain elongation by reversible phosphorylation

Craney

Kelly

Jia

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Most metazoan E3 ligases contain a signature RING domain that promotes the transfer of ubiquitin from the active site of E2 conjugating enzymes to lysine residues in substrates. Although these RING-E3s depend on E2 enzymes for catalysis, how they turn on their E2s at the right time and place remains poorly understood. Here we report a phosphorylation-dependent mechanism that ensures timely activation of the E2 Ube2S by its RING-E3, the anaphase-promoting complex (APC/C); while phosphorylation of a specific serine residue in the APC/C coactivator Cdc20 prevents delivery of Ube2S to the APC/C, removal of this mark by PP2A B56 allows Ube2S to bind the APC/C and catalyze ubiquitin chain elongation. PP2AB56 also stabilizes kinetochore-microtubule attachments to shut off the spindle checkpoint, suggesting that cells regulate the E2-E3 interplay to coordinate ubiquitination with critical events during cell division.ubiquitin | anaphase-promoting complex | APC/C | Ube2S | phosphorylation

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Section: Discussionmentioning

confidence: 71%

Control of APC/C-dependent ubiquitin chain elongation by reversible phosphorylation

Craney

Kelly

Jia

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…For example, if ubiquitination of mitotic targets were both spatially regulated and closely coupled to degradation, local regulation of proteasomes could also modulate their destruction. This is an attractive idea, particularly because activation of the anaphase promoting complex, a major mitotic ubiquitin ligase, is coupled to chromosome localization (Sivakumar et al, 2014), where we likewise observe SUMOylated Psmd1 (Figure S2). Further work will clearly be needed to test these possibilities.…”

Section: Resultsmentioning

confidence: 88%

SUMOylation of Psmd1 Controls Adrm1 Interaction with the Proteasome

Ryu¹,

Gygi²,

Azuma³

et al. 2014

Cell Reports

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SUMOylation is the covalent conjugation of SUMO polypeptides to cellular target proteins. Psmd1 is a subunit of the proteasomal 19S regulatory particle that acts as a docking site for Adrm1, another proteasome subunit that recruits ubiquitinated substrates for proteolysis. Here, we show that the SUMO deconjugating enzyme xSENP1 specifically interacts with Psmd1, and that disruption of xSENP1 targeting delays mitotic exit. Psmd1 becomes SUMOylated through the action of the SUMO E3 enzyme PIASy. We mapped SUMOylation sites within Psmd1, and find that SUMOylation of a critical lysine immediately adjacent to the Adrm1 binding domain regulates Adrm1 association with Psmd1. Together, our findings suggest that the interaction of Psmd1 with Adrm1 is controlled by SUMOylation in a manner that may alter proteasome composition and function. These findings demonstrate a new mechanism for regulation of ubiquitin-mediated protein degradation by ubiquitin-like proteins of the SUMO family.

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“…Here, we further demonstrated that SKA3 protein was progressively up-regulated during progression from adenoma to carcinoma within individual patients. SKA3 is a subunit located in the kinetochore outer layer of the SKA complex, which works together with the NDC80 complex to control and promote proper mitotic exit during mitosis [36, 37]. Depletion of SKA3 induces mitotic arrest in HeLa cells [28, 29].…”

Section: Discussionmentioning

confidence: 99%

Over-expression of AURKA, SKA3 and DSN1 contributes to colorectal adenoma to carcinoma progression

et al. 2016

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Development of colorectal cancer (CRC) involves sequential transformation of normal mucosal tissues into benign adenomas and then adenomas into malignant tumors. The identification of genes crucial for malignant transformation in colorectal adenomas (CRAs) has been based primarily on cross-sectional observations. In this study, we identified relevant genes using autologous samples. By performing genome-wide SNP genotyping and RNA sequencing analysis of adenocarcinomas, adenomatous polyps, and non-neoplastic colon tissues (referred as tri-part samples) from individual patients, we identified 68 genes with differential copy number alterations and progressively dysregulated expression. Aurora A, SKA3, and DSN1 protein levels were sequentially up-regulated in the samples, and this overexpression was associated with chromosome instability (CIN). Knockdown of SKA3 in CRC cells dramatically reduced cell growth rates and increased apoptosis. Depletion of SKA3 or DSN1 induced G2/M arrest and decreased migration, invasion, and anchorage-independent growth. AURKA and DSN1 are thus critical for chromosome 20q amplification-associated malignant transformation in CRA. Moreover, SKA3 at chromosome 13q was identified as a novel gene involved in promoting malignant transformation. Evaluating the expression of these genes may help identify patients with progressive adenomas, helping to improve treatment.

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The spindle and kinetochore–associated (Ska) complex enhances binding of the anaphase-promoting complex/cyclosome (APC/C) to chromosomes and promotes mitotic exit

Abstract: Cells depleted of Ska arrest at metaphase. Chromosome-associated APC/C shows high ubiquitylation activity. Ska complex helps to localize APC/C on chromosomes. Forced localization of Ska complex to kinetochores enhances APC/C localization to chromosomes and promotes APC/C activity.

Cited by 67 publications

References 46 publications

Control of APC/C-dependent ubiquitin chain elongation by reversible phosphorylation

Control of APC/C-dependent ubiquitin chain elongation by reversible phosphorylation

SUMOylation of Psmd1 Controls Adrm1 Interaction with the Proteasome

Over-expression of AURKA, SKA3 and DSN1 contributes to colorectal adenoma to carcinoma progression

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