Mps1 is SUMO-modified during the cell cycle

Restuccia, A.; Yang, Fan; Chen, Changyan; Lu, Lihua; Dai, Wei

doi:10.18632/oncotarget.6552

Cited by 11 publications

(8 citation statements)

References 48 publications

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“…Mps1, a member of the spindle-monitoring complex, is involved in centrosome duplication and spindle checkpoint (33) and cell cycle regulation, and has maximum kinase activity in the M phase of the cell cycle (34). Typically, Mps1 is an unstable protein, which is degraded by the ubiquitin-proteasome pathway when centrosome duplication is completed, and cells enter anaphase (35).…”

Section: Discussionmentioning

confidence: 99%

Mps1 is associated with the BRAFV600E mutation and predicts poor outcome in patients with colorectal cancer

et al. 2019

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Colorectal cancer (CRC) with the V600E mutation of B-Raf proto-oncogene serine/threonine kinase (BRAF V600E ) mutation is insensitive to chemotherapy and is indicative of a poor patient prognosis. Although BRAF inhibitors have a marked effect on malignant melanoma harboring the BRAF V600E mutation, they have a limited effect on patients with CRC with the same BRAF mutation. A previous study identified a novel gene, monopolar spindle protein kinase 1 (Mps1), a downstream target of BRAF V600E only, rather than of wild-type BRAF as well, which contributes to tumorigenesis in melanoma. In the present study, the incidence of BRAF V600E in patients with CRC was identified and the correlation of Mps1, phospho-extracellular-signal-regulated kinase (p-ERK) and BRAF V600E was investigated. The results indicated that the mutation rate of BRAF V600E was 5.2% in CRC. Poorly differentiated tumors and mucinous tumors have a significantly higher incidence of BRAF V600E compared with well-differentiated tumors and non-mucinous tumors (P<0.05). Kaplan-Meier survival analysis indicated that the survival rate was markedly lower in patients with BRAF V600E compared with in patients with wild-type BRAF (BRAF WT ). The expression of p-ERK and Mps1 in CRC with BRAF V600E was significantly higher compared with in CRC with BRAF WT (P<0.05), and their expression is associated with cancer classification, degree of differentiation and lymph node transfusion (P<0.05). In addition p-ERK expression was positively correlated with Mps1 expression, with a contingency coefficient of 0.679 (P=0.002). In conclusion, the results of the present study indicated that Mps1 was significantly associated with BRAF V600E /p-ERK and may serve a crucial function in the development of CRC. The results of the present study raise the possibility that targeting the oncogenic BRAF and Mps1, particularly when in conjunction, could provide promising therapeutic opportunities for the treatment of CRC.

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Section: Discussionmentioning

confidence: 99%

Mps1 is associated with the BRAFV600E mutation and predicts poor outcome in patients with colorectal cancer

et al. 2019

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“…Among these are centromeric proteins Cse4, Cep3, Ndc10 in yeast, and CENPI [35,40,41], the helicase PICH [42], and the centromere-associated kinase Aurora B/AURKB along with its partners Borealin/CDCA8, MIS18BP1 and Survivin/BIRC5 (Bir1 in S. cerevisiae ) in mammalian cells [35,43,44,45,46]. At the level of the outer kinetochore, one finds SUMOylated Ndc80 and NUF2 [35,36], as well as the kinesins CENPE/KIF10 [36] and KIF18A [47], the RNA binding protein NKAP [48], the Ran GTPase activating protein RanGAP1 [49], the ANAPC4 subunit of the APC/C [50,51], along with the protein kinases BUB1B/BubR1 [52] and MPS1/TTK [53]. When known, most of these proteins are SUMOylated by SUMO2/3, and often require PIAS4 (also known as PIASγ) as a E3 SUMO ligase (see Table 1).…”

Section: Sumo Targetsmentioning

confidence: 99%

How Does SUMO Participate in Spindle Organization?

Abrieu

Liakopoulos

2019

Cells

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The ubiquitin-like protein SUMO is a regulator involved in most cellular mechanisms. Recent studies have discovered new modes of function for this protein. Of particular interest is the ability of SUMO to organize proteins in larger assemblies, as well as the role of SUMO-dependent ubiquitylation in their disassembly. These mechanisms have been largely described in the context of DNA repair, transcriptional regulation, or signaling, while much less is known on how SUMO facilitates organization of microtubule-dependent processes during mitosis. Remarkably however, SUMO has been known for a long time to modify kinetochore proteins, while more recently, extensive proteomic screens have identified a large number of microtubule- and spindle-associated proteins that are SUMOylated. The aim of this review is to focus on the possible role of SUMOylation in organization of the spindle and kinetochore complexes. We summarize mitotic and microtubule/spindle-associated proteins that have been identified as SUMO conjugates and present examples regarding their regulation by SUMO. Moreover, we discuss the possible contribution of SUMOylation in organization of larger protein assemblies on the spindle, as well as the role of SUMO-targeted ubiquitylation in control of kinetochore assembly and function. Finally, we propose future directions regarding the study of SUMOylation in regulation of spindle organization and examine the potential of SUMO and SUMO-mediated degradation as target for antimitotic-based therapies.

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“…Ubc9 regulates SUMO target discrimination and can bind specifically to lysine residues in a nonconsensus SUMO modification motif [17, 27, 28]. There is a single residue in the VP55 coiled-coil domain at position 87 (Lys87), suggesting that Lys87 may be involved in Ubc9 binding.…”

Section: Resultsmentioning

confidence: 99%

Orthoreovirus outer-fiber proteins are substrates for SUMO-conjugating enzyme Ubc9

Wang

et al. 2016

Oncotarget

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Reoviruses are potential anticancer agents due to their ability to induce cell death in tumor cells. Grass carp reovirus (GCRV) is one of the best characterized models on reovirus pathogenesis in vitro. However, there is little known about how SUMOylation affects reovirus pathogenesis. The SUMO conjugating enzyme 9 (Ubc9) determines the targets of SUMOylation. Here, the protein interactions between reovirus outer fiber proteins, specifically GCRV-104 VP55, and Ubc9 were probed using a yeast two-hybrid system. The N-terminal coiled-coil domain of VP55, containing a single lysine residue, was responsible for the interaction between VP55 and Ubc9 in yeast. In solid phase binding assays, a single amino acid mutation (K87R) prevented Ubc9 from binding to VP55. Overexpression of Ubc9 enhanced GCRV-104 infection efficiency, and knockdown of Ubc9 in CIK cells inhibited viral replication, which suggested that Ubc9 was a proviral factor. Furthermore, Ubc9 was shown to bind outer fiber proteins from type II GCRV, avian reovirus and mammalian reovirus in yeast. To our knowledge, this is the first study to show that Ubc9 binds to reovirus outer-fiber proteins and likely contributes to efficient orthoreovirus replication. These results suggest that SUMOylation modifications could be targeted to improve the therapeutic efficacy of oncolytic reovirus.

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Mps1 is SUMO-modified during the cell cycle

Cited by 11 publications

References 48 publications

Mps1 is associated with the BRAFV600E mutation and predicts poor outcome in patients with colorectal cancer

Mps1 is associated with the BRAFV600E mutation and predicts poor outcome in patients with colorectal cancer

How Does SUMO Participate in Spindle Organization?

Orthoreovirus outer-fiber proteins are substrates for SUMO-conjugating enzyme Ubc9

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