Mitosin/CENP-F as a Negative Regulator of Activating Transcription Factor-4

Zhou, Xubin; Wang, Rong; Фан, Ли; Li, Yán; Ma, Li; Yang, Ziqing; Yu, Wei; Jing, Naihe; Zhu, Xueliang

doi:10.1074/jbc.m414310200

Cited by 30 publications

(29 citation statements)

References 48 publications

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“…CENP-F regulates gene transcription and proliferation through association with the transcription factor ATF4. 50 Our results suggest that CENP-F may be a potential candidate for Ets-2 co-transcriptional regulation.…”

Section: Discussionmentioning

confidence: 79%

CENP‐F expression is associated with poor prognosis and chromosomal instability in patients with primary breast cancer

O’Brien

Fagan

Fox

et al. 2007

Intl Journal of Cancer

106

102

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DNA microarrays have the potential to classify tumors according to their transcriptome. Tissue microarrays (TMAs) facilitate the validation of biomarkers by offering a high‐throughput approach to sample analysis. We reanalyzed a high profile breast cancer DNA microarray dataset containing 96 tumor samples using a powerful statistical approach, between group analyses. Among the genes we identified was centromere protein‐F (CENP‐F), a gene associated with poor prognosis. In a published follow‐up breast cancer DNA microarray study, comprising 295 tumour samples, we found that CENP‐F upregulation was significantly associated with worse overall survival (p < 0.001) and reduced metastasis‐free survival (p < 0.001). To validate and expand upon these findings, we used 2 independent breast cancer patient cohorts represented on TMAs. CENP‐F protein expression was evaluated by immunohistochemistry in 91 primary breast cancer samples from cohort I and 289 samples from cohort II. CENP‐F correlated with markers of aggressive tumor behavior including ER negativity and high tumor grade. In cohort I, CENP‐F was significantly associated with markers of CIN including cyclin E, increased telomerase activity, c‐Myc amplification and aneuploidy. In cohort II, CENP‐F correlated with VEGFR2, phosphorylated Ets‐2 and Ki67, and in multivariate analysis, was an independent predictor of worse breast cancer‐specific survival (p = 0.036) and overall survival (p = 0.040). In conclusion, we identified CENP‐F as a biomarker associated with poor outcome in breast cancer and showed several novel associations of biological significance. © 2006 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 79%

CENP‐F expression is associated with poor prognosis and chromosomal instability in patients with primary breast cancer

O’Brien

Fagan

Fox

et al. 2007

Intl Journal of Cancer

106

102

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“…One possibility is that Cenp-F degradation plays roles in contexts outside of mitosis. For example, Cenp-F inhibits the transcription factor ATF4 (Zhou et al, 2005), which has been implicated in numerous post-mitotic phenomenon including long-term memory and synaptic plasticity (Ameri and Harris, 2008). Cenp-F can also bind to Rb (Rattner et al, 1993), which apart from its well-characterised role in the cell cycle, also activates transcription of muscle-specific genes (Novitch et al, 1996;Novitch et al, 1999).…”

Section: The Role Of Cenp-f Degradationmentioning

confidence: 99%

Cdc20 is required for the post-anaphase, KEN-dependent degradation of centromere protein F

Gurden

Holland

Zon

et al. 2010

Journal of Cell Science

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Progression through mitosis and cytokinesis requires the sequential proteolysis of several cell-cycle regulators. This proteolysis is mediated by the ubiquitin-proteasome system, with the E3 ligase being the anaphase-promoting complex, also known as the cyclosome (APC/C). The APC/C is regulated by two activators, namely Cdc20 and Cdh1. The current view is that prior to anaphase, the APC/C is activated by Cdc20, but that following anaphase, APC/C switches to Cdh1-dependent activation. However, here we present an analysis of the kinetochore protein Cenp-F that is inconsistent with this notion. Although it has long been appreciated that Cenp-F is degraded sometime during or after mitosis, exactly when and how has not been clear. Here we show that degradation of Cenp-F initiates about six minutes after anaphase, and that this is dependent on a C-terminal KEN-box. Although these two observations are consistent with Cenp-F being a substrate of Cdh1-activated APC/C, Cenp-F is degraded normally in Cdh1-null cells. By contrast, RNAi-mediated repression of APC/C subunits or Cdc20 does inhibit Cenp-F degradation. These findings therefore suggest that the APC/C does not simply ‘switch’ upon anaphase onset; rather, our observations indicate that Cdc20 also contributes to post-anaphase activation of the APC/C. We also show that the post-anaphase, KEN-box-dependent degradation of Cenp-F requires it to be farnesylated, a post-translational modification usually linked to membrane association. Because so many of the behaviours of Cenp-F are farnesylation-dependent, we suggest that this modification plays a more global role in Cenp-F function.

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“…CENPF is a large human protein (O350 kDa; 3113 amino acids), which plays a crucial role in cell division by controlling microtubule dynamics, maintaining chromosome condensation, transcription regulation, and cell cycle progression (Liao et al 1995, Zhu et al 1995, Holt et al 2005, Zhou et al 2005. It is expressed and localized in a cell-cycle-dependent manner (Liao et al 1995, Zhu et al 1995.…”

Section: Introductionmentioning

confidence: 99%

Silencing CENPF in bovine preimplantation embryo induces arrest at 8-cell stage

Toralova¹,

Šušor²,

Němcová³

et al. 2009

Reproduction

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Identification of genes that are important for normal preimplantation development is essential for understanding the basics of early mammalian embryogenesis. In our previous study, we have shown that CENPF (mitosin) is differentially expressed during preimplantation development of bovine embryos. CENPF is a centromere-kinetochore complex protein that plays a crucial role in the cell division of somatic cells. To our best knowledge, no study has yet been done on either bovine model, or oocytes and preimplantation embryos. In this study, we focused on the fate of bovine embryos after injection of CENPF double-stranded RNA (dsRNA) into the zygotes. An average decrease of CENPF mRNA abundance by 94.9% or more and an extensive decline in immunofluorescence staining intensity was detected relative to controls. There was no disparity between individual groups in the developmental competence before the 8-cell stage. However, the developmental competence rapidly decreased then and only 28.1% of CENPF dsRNA injected 8-cell embryos were able to develop further (uninjected control: 71.8%; green fluorescent protein dsRNA injected control: 72.0%). In conclusion, these results show that depletion of CENPF mRNA in preimplantation bovine embryos leads to dramatic decrease of developmental competence after embryonic genome activation.

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Mitosin/CENP-F as a Negative Regulator of Activating Transcription Factor-4

Cited by 30 publications

References 48 publications

CENP‐F expression is associated with poor prognosis and chromosomal instability in patients with primary breast cancer

CENP‐F expression is associated with poor prognosis and chromosomal instability in patients with primary breast cancer

Cdc20 is required for the post-anaphase, KEN-dependent degradation of centromere protein F

Silencing CENPF in bovine preimplantation embryo induces arrest at 8-cell stage

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