Cdc48 is required for the stability of Cut1/separase in mitotic anaphase

Ikai, Nobuyasu; Yanagida, Mitsuhiro

doi:10.1016/j.jsb.2006.04.003

Cited by 25 publications

(45 citation statements)

References 64 publications

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“…In budding yeast, Cdc48 is important for passing Start, the cell cycle commitment point in G1, by degrading the G1-cyclindependent kinase inhibitor Far1 (Fu et al, 2003). In fission yeast, Cdc48 is required for the metaphase-to-anaphase transition by stabilizing Separase (Ikai and Yanagida, 2006), the enzyme that cleaves cohesin components to separate sister chromatids (Uhlmann et al, 1999). In addition, Cdc48/p97 together with Npl4-Ufd1 has been shown to be involved in spindle disassembly during mitotic exit in both budding yeast and Xenopus egg extracts (Cao et al, 2003), although the results are controversial (Heubes and Stemmann, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…It remains a possibility that Cdc48-Shp1 controls the proteolytic steps for proper duplication and separation of the SPB/centrosome. In addition to a function at the SPB, it has been shown that a specific mutation of cdc48 in fission yeast causes metaphase arrest by destabilizing Separase (Ikai and Yanagida, 2006), the enzyme that cleaves cohesin components to separate sister chromatids (Uhlmann et al, 1999). In our cdc48-3 mutant, the level of Separase is similar to that in wild-type cells (data not shown).…”

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confidence: 99%

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The AAA-ATPase Cdc48 and cofactor Shp1 promote chromosome bi-orientation by balancing Aurora B activity

Cheng

Chen

2010

Journal of Cell Science

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SummaryThe assembly, disassembly and dynamic movement of macromolecules are integral to cell physiology. The ubiquitin-selective chaperone Cdc48 (p97 in Metazoa), an AAA-ATPase, might facilitate such processes in the cell cycle. Cdc48 in budding yeast was initially isolated from a mitotic mutant. However, its function in mitosis remained elusive. Here we show that the temperature-sensitive cdc48-3 mutant and depletion of cofactor Shp1 (p47 in Metazoa) cause cell-cycle arrest at metaphase. The arrest is due to a defect in bipolar attachment of the kinetochore that activates the spindle checkpoint. Furthermore, Cdc48-Shp1 positively regulates Glc7/protein phosphatase 1 by facilitating nuclear localization of Glc7, whereas it opposes Ipl1/Aurora B kinase activity. Thus, we propose that Cdc48-Shp1 promotes nuclear accumulation of Glc7 to counteract Ipl1 activity. Our results identify Cdc48 and Shp1 as critical components that balance the kinase and phosphatase activities at the kinetochore in order to achieve stable bipolar attachment.Key words: Kinetochore, Mitosis, Saccharomyces cerevisiae, AAA-ATPase, Cdc48 Journal of Cell ScienceMitosis must be executed with a precise order to evenly segregate sister chromatids. A critical step in this process is the assembly of kinetochores at the centromere and binding of sister kinetochores to microtubules emanating from the opposite spindle poles. The attachment of sister kinetochores to microtubules from the same pole is corrected by Aurora B protein kinase (Ipl1 in budding yeast), that promotes turnover of microtubules from improperly attached kinetochores (Pinsky et al., 2006b;Tanaka et al., 2002). Once all kinetochores have established bipolar attachment, the cell can then enter anaphase to segregate sister chromatids. Anaphase is triggered by the E3 ubiquitin protein ligase Anaphase-promoting complex/cyclosome (APC/C) ( Thornton and Toczyski, 2006). By binding to the activator-adaptor Cdc20, APC/C targets the anaphase inhibitor Securin (Pds1 in budding yeast) for degradation, leading to cleavage of the cohesin complex and separation of sister chromatids (Yu, 2007). Later in anaphase, APC/C is coupled with another adaptor Cdh1 to target the degradation of Cdc20 and mitotic cyclins for mitotic exit (Huang et al., 2001;Schwab et al., 2001). The presence of any unattached kinetochore triggers the spindle checkpoint to inhibit APC/C-Cdc20, thus blocking anaphase onset (Burke and Stukenberg, 2008). In addition, budding yeast at metaphase normally aligns the spindle along the mother-bud axis with the nucleus positioned at the bud neck, so that the nucleus divides into both the mother and the bud after anaphase. A misoriented spindle triggers the spindle position checkpoint, composed of the checkpoint proteins Bub2 and Bfa1, to inhibit APC/C-Cdh1, thus blocking mitotic exit (Fraschini et al., 2008).To better understand the function of Cdc48/p97 in the cell cycle, we examined the phenotypes of the cdc48-3 mutant in budding yeast. We show that the mutant arrests at metaphase as a...

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

The AAA-ATPase Cdc48 and cofactor Shp1 promote chromosome bi-orientation by balancing Aurora B activity

Cheng

Chen

2010

Journal of Cell Science

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“…Gene disruption of CDC48/p97 in budding and fission yeasts (Saccharomyces cerevisiae and Schizosaccharomyces pombe; Frö hlich et al, 1991; Ikai and Yanagida, 2006), trypanosomes (TbVCP; Lamb et al, 2001), mouse (Muller et al, 2007), and Drosophila (ter94; Leon and McKearin, 1999) demonstrates that CDC48/p97 is essential in unicellular and multicellullar organisms. At the molecular level, CDC48/p97 is involved in many distinct cellular processes (Woodman, 2003;Dreveny et al, 2004;Meyer, 2005;Jentsch and Rumpf, 2007).…”

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confidence: 99%

In Planta Analysis of the Cell Cycle-Dependent Localization of AtCDC48A and Its Critical Roles in Cell Division, Expansion, and Differentiation

2008

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CDC48/p97 is a conserved homohexameric AAA-ATPase chaperone required for a variety of cellular processes but whose role in the development of a multicellular model system has not been examined. Here, we have used reverse genetics, visualization of a functional Arabidopsis (Arabidopsis thaliana) CDC48 fluorescent fusion protein, and morphological analysis to examine the subcellular distribution and requirements for AtCDC48A in planta. Homozygous Atcdc48A T-DNA insertion mutants arrest during seedling development, exhibiting decreased cell expansion and displaying pleiotropic defects in pollen and embryo development. Atcdc48A insertion alleles show significantly reduced male transmission efficiency due to defects in pollen tube growth. Yellow fluorescent protein-AtCDC48A, a fusion protein that functionally complements the insertion mutant defects, localizes in the nucleus and cytoplasm and is recruited to the division mid-zone during cytokinesis. The pattern of nuclear localization differs according to the stage of the cell cycle and differentiation state. Inducible expression of an Atcdc48A Walker A ATPase mutant in planta results in cytokinesis abnormalities, aberrant cell divisions, and root trichoblast differentiation defects apparent in excessive root hair emergence. At the biochemical level, our data suggest that the endogenous steady-state protein level of AtCDC48A is dependent upon the presence of ATPase-active AtCDC48A. These results demonstrate that CDC48A/p97 is critical for cytokinesis, cell expansion, and differentiation in plants.Members of the AAA (ATPase associated with different cellular activities)-ATPase protein family are characterized by either one (type I) or two (type II) 220 to 250 amino acid ATPase domains containing both conserved Walker A and B motifs per protomer (Beyer, 1997;Neuwald et al., 1999). The ATPase domains elicit protein conformational changes upon the nucleotide binding, hydrolysis, and product release that is believed to be required for the function of the mechanochemical enzyme (Rouiller et al

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“…This strongly implicates Cdc48 in sister chromatid disjunction and segregation, and suggested that Cdc48 is a positive regulator of separase and thus cohesin cleavage. In support of this notion, the cdc48 mutation led to instability of Cut1/separase [22]. Curiously, however, separase was destabilized mostly in anaphase, and this was apparently in a proteasomeindependent fashion.…”

Section: Evidence In Yeastmentioning

confidence: 85%

Role(s) of Cdc48/p97 in mitosis

Meyer¹,

Popp

2008

Biochemical Society Transactions

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The ubiquitin-dependent chaperone Cdc48 (cell division cycle 48)/p97 is involved in a variety of degradative and regulatory processes during interphase that help to maintain cellular homoeostasis. The results available so far suggest that its basic activity is to mobilize ubiquitinated substrate proteins from cellular structures or segregate them from binding partners, and then hand them over for degradation or recycling. Several studies in different organisms show that Cdc48/p97 also has critical roles in mitosis. However, many important aspects of these functions and the general perspective have remained unclear.

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Cdc48 is required for the stability of Cut1/separase in mitotic anaphase

Cited by 25 publications

References 64 publications

The AAA-ATPase Cdc48 and cofactor Shp1 promote chromosome bi-orientation by balancing Aurora B activity

The AAA-ATPase Cdc48 and cofactor Shp1 promote chromosome bi-orientation by balancing Aurora B activity

In Planta Analysis of the Cell Cycle-Dependent Localization of AtCDC48A and Its Critical Roles in Cell Division, Expansion, and Differentiation

Role(s) of Cdc48/p97 in mitosis

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