PMID:28410192

Citation	'Park, J, Park, HY, Kim, S, Kim, HS, Park, JY, Go, H and Lee, CW (2017) Pellino 1 inactivates mitotic spindle checkpoint by targeting BubR1 for ubiquitinational degradation. Oncotarget '
Abstract	Aberrant constitutive activation of receptor-mediated downstream signalling plays an active role in the deregulation of cell cycle control. The mitotic spindle checkpoint is important in preventing abnormal mitotic cell cycle with chromosome missegregation from achieving neoplastic aneuploidy. However, mechanisms coupling receptor-mediated signalling to mitotic spindle checkpoint regulation remain unclear. Pellino 1 is a receptor signal-responsive E3 ubiquitin ligase, and the application of certain receptor-mediated signalling regulates the expression and activity of Pellino 1. In the present study, Pellino 1 expression induced extensive chromosome aneuploidy and allowed abnormal mitotic cells to adapt and become aneuploid in vitro and in vivo. Pellino 1 directly interacted with BubR1, a key component of mitotic spindle checkpoint, in a mitotic cell-cycle dependent manner, and down-regulated the stability of BubR1 by ubiquitination-mediated degradation and induced mitotic dysfunction. In summary, Pellino 1 expression acts as an inhibitory signal of the homeostatic regulation of mitotic cell cycle and checkpoint, and thus contributes to the initiation and progression of neoplastic chromosome aneuploidy.
Links	PubMed Online version:10.18632/oncotarget.16762
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:PELI1		GO:0000778: condensed nuclear chromosome kinetochore	ECO:0000314:		C		Protein: E3 ubiquitin-protein ligase pellino homolog 1 Organism: Mouse Immunofluorescence analyses revealed localization of Peli1 at spindle poles and kinetochores (Figure 2A).	complete CACAO 12844
MOUSE:PELI1		GO:0051306: mitotic sister chromatid separation	ECO:0000315:		P		The metaphase chromosome-spreading assay revealed that premature sister chromatid separation (PMSCS), a hallmark of a defective mitotic checkpoint [19, 25], was observed in approximately 18 ± 1.7% of splenocytes isolated from Peli1-Tg mice but in < 5% of control splenocytes (Figure 1B), by author. Protein: E3 ubiquitin-protein ligase pellino homolog 1 Organism: mouse	complete CACAO 12836
MOUSE:PELI1		GO:0048536: spleen development	ECO:0000315:		P		Protien: E3 ubiquitin-protein ligase pellino homolog 1 Organism: Mouse splenocytes were isolated from Peli1-Tg mice that displayed splenic plasmacytoid differentiation and lymphomas, and from control littermate non-Tg mice that had normal splenic features (Figure 1A, 1B) by author.	complete CACAO 12837
MOUSE:PELI1		GO:1905558: negative regulation of mitotic nuclear envelope disassembly	ECO:0000314:		P		Organism: mouse Protein:E3 ubiquitin-protein ligase pellino homolog 1 Peli1 overexpressing cells showed severe delays in the metaphase-to-anaphase transition compared to control cells. (B) Average time from mitotic onset (nuclear envelope breakdown) to anaphase of Peli1 overexpressing cells or control cells (control cells, n = 24; Myc-Peli1-transfected cells, n = 20).	complete CACAO 12845

References

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