The Dissociation of Cohesin from Chromosomes in Prophase Is Regulated by Polo-like Kinase

Sumara, Izabela; Vorlaufer, Elisabeth; Stukenberg, P. Todd; Kelm, Olaf; Redemann, Norbert; Nigg, Erich A.; Peters, Jan‐Michael

doi:10.1016/s1097-2765(02)00473-2

Cited by 411 publications

(372 citation statements)

References 31 publications

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“…Moreover, a recent study suggests that PLK1 is able to phosphorylate Cyclin B1 (Jackman et al, 2003) directly, and that specific phosphorylation cooperated with other signals in the nuclear import of Cyclin protein, a crucial checkpoint for the initiation of mitosis (Yuan et al, 2002). Later in mitosis, PLK1 has been implicated in the regulation of the anaphasepromoting complex (Kotani et al, 1998;Golan et al, 2002), centrosome maturation and destructions of cohesins (Sumara et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Polo-like kinase isoform expression is a prognostic factor in ovarian carcinoma

Weichert

Denkert

Schmidt³

et al. 2004

Br J Cancer

163

131

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The Polo-like kinase (PLK) family comprises three serine/threonine kinases, functionally involved in signal transduction pathways essential for the accomplishment of mitosis in both normal and malignant cells. Moreover, certain PLKs have been functionally linked to cytoskeletal reorganisation. In this study, the expression of PLK1 and PLK3 was determined immunohistochemically in tissue specimen of normal ovaries (n ¼ 9), cystadenomas (n ¼ 17), borderline tumours (n ¼ 13) and ovarian carcinomas (n ¼ 77). PLK 1 and PLK3 expression was low in normal ovarian surface epithelium and borderline tumours, with moderately higher expression levels in cystadenomas. In ovarian carcinomas, 26% of cases were PLK1 positive and 50.6% of cases were PLK3 positive. A positive correlation of both PLK1 and PLK3 expression with indicators of mitotic frequency could be established. The overexpression of either isoenzyme had an impact on patient prognosis with shortened survival time for patients with tumours positive for PLK1 (P ¼ 0.02) and PLK3 (P ¼ 0.02), but only PLK1 expression remained a prognostic factor in multivariate survival analysis (P ¼ 0.03). The results of this study, if interpreted in the context of recently published functional data, suggest that inhibition of PLKs might represent an interesting new targeted approach for chemotherapy of epithelial ovarian cancer. Furthermore, this study suggests that PLK1 is a novel independent prognostic marker in ovarian carcinomas.

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Section: Discussionmentioning

confidence: 99%

Polo-like kinase isoform expression is a prognostic factor in ovarian carcinoma

Weichert

Denkert

Schmidt³

et al. 2004

Br J Cancer

163

131

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“…It was shown that cohesin dissociates from chromosomes before metaphase, which requires the Plk1 (Sumara et al, 2002). A recent study revealed that Rad21/Scc1 and SA2/ Scc3 are the major targets of Plk1 (Hauf et al, 2005).…”

Section: Mitosis-specific Activity Of Cohesin At the Spindle Polesmentioning

confidence: 99%

Cohesin Associates with Spindle Poles in a Mitosis-specific Manner and Functions in Spindle Assembly in Vertebrate Cells

Kong

Ball

Sonoda

et al. 2009

MBoC

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Cohesin is an essential protein complex required for sister chromatid cohesion. Cohesin associates with chromosomes and establishes sister chromatid cohesion during interphase. During metaphase, a small amount of cohesin remains at the chromosome-pairing domain, mainly at the centromeres, whereas the majority of cohesin resides in the cytoplasm, where its functions remain unclear. We describe the mitosis-specific recruitment of cohesin to the spindle poles through its association with centrosomes and interaction with nuclear mitotic apparatus protein (NuMA). Overexpression of NuMA enhances cohesin accumulation at spindle poles. Although transient cohesin depletion does not lead to visible impairment of normal spindle formation, recovery from nocodazole-induced spindle disruption was significantly impaired. Importantly, selective blocking of cohesin localization to centromeres, which disrupts centromeric sister chromatid cohesion, had no effect on this spindle reassembly process, clearly separating the roles of cohesin at kinetochores and spindle poles. In vitro, chromosome-independent spindle assembly using mitotic extracts was compromised by cohesin depletion, and it was rescued by addition of cohesin that was isolated from mitotic, but not S phase, cells. The combined results identify a novel spindle-associated role for human cohesin during mitosis, in addition to its function at the centromere/kinetochore regions. INTRODUCTIONMitotic spindle formation is critical for proper chromosome congression, alignment, and segregation during cell division (Compton, 2000;Scholey et al., 2003;Kline-Smith and Walczak, 2004). Microtubules (MTs) undergo drastic changes in their dynamics and organization as the cell enters mitosis to form the bipolar spindle apparatus. As the nuclear membrane breaks down at the G2/M transition, interphase cytoskeletal MTs are destabilized, and mitotic spindle MTs nucleate from two opposing centrosomes/spindle poles with increased growth and turnover rates (Saxton et al., 1984;Zhai et al., 1996). This mitosis-specific change of microtubule behavior indicates the presence of cell cycle-specific regulators of spindles. Indeed, studies identified many important microtubule-associated proteins (MAPs) that regulate different aspects of mitotic spindle dynamics, such as the efficiency of MT nucleation and minus-end focusing at spindle poles, MT plus-and minus-end dynamics, and overall spindle stability (Kline-Smith and Walczak, 2004). However, the intricate regulatory mechanisms for spindle organization are not completely understood, and there are most likely additional factors that contribute to proper spindle regulation during mitosis.Cohesin is a conserved and essential multiprotein complex required for sister chromatid cohesion (Losada et al., 1998;Uhlmann and Nasmyth, 1998;Toth et al., 1999). Genetic studies in both yeast and metazoans revealed that inhibition of cohesin function leads to premature separation of sister chromatids, chromosome misalignment, and meloteric attachment of spindles to...

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“…This population is essential in preventing precocious separation of the sister chromatids and allowing proper chromosome alignment (Vass et al 2003;Vagnarelli et al 2004;. The dissociation of cohesin in prophase requires Polo and Aurora B kinases as well as a number of additional factors that include Wapl Sumara et al 2002;Hauf et al 2005;Gandhi et al 2006;Kueng et al 2006). At the onset of anaphase, cleavage of Scc1/Rad21 by separase drives dissociation of the remaining cohesin and sister chromatid separation ensues (Hauf et al 2001).…”

Section: Introductionmentioning

confidence: 99%