Cdc25 and the importance of G<sub>2</sub>control

Bouldin, Cortney M.; Kimelman, David

doi:10.4161/cc.29537

Cited by 49 publications

(27 citation statements)

References 49 publications

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“…Furthermore, the lengthening of G 1 phase not only avoids two compatible events regarding mitosis and morphogenesis46, but permit changes of epigenetic marks and nuclear architecture to determine cell fates4748. While many researches were emphasized on the regulation of G 1 phase, a few studies have begun to shed light on the G 2 phase regulation lately49. In chordates, a longer G 2 phase, which was introduced into epidermal cells flanking the neural plate, was found to be necessary for neural tube closure50.…”

Section: Discussionmentioning

confidence: 99%

Stathmin-like 4 is critical for the maintenance of neural progenitor cells in dorsal midbrain of zebrafish larvae

Lin

Lee

2016

Sci Rep

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A delicate balance between proliferating and differentiating signals is necessary to ensure proper growth and neuronal specification. By studying the developing zebrafish brain, we observed a specific and dynamic expression of a microtubule destabilizer gene, stathmin-like 4 (stmn4), in the dorsal midbrain region. The expression of stmn4 was mutually exclusive to a pan-neuronal marker, elavl3 that indicates its role in regulating neurogenesis. We showed the knockdown or overexpression of stmn4 resulted in premature neuronal differentiation in dorsal midbrain. We also generated stmn4 maternal-zygotic knockout zebrafish by the CRISPR/Cas9 system. Unexpectedly, only less than 10% of stmn4 mutants showed similar phenotypes observed in that of stmn4 morphants. It might be due to the complementation of the increased stmn1b expression observed in stmn4 mutants. In addition, time-lapse recordings revealed the changes in cellular proliferation and differentiation in stmn4 morphants. Stmn4 morphants displayed a longer G2 phase that could be rescued by Cdc25a. Furthermore, the inhibition of Wnt could reduce stmn4 transcripts. These results suggest that the Wnt-mediated Stmn4 homeostasis is crucial for preventing dorsal midbrain from premature differentiation via the G2 phase control during the neural keel stage.

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Section: Discussionmentioning

confidence: 99%

Stathmin-like 4 is critical for the maintenance of neural progenitor cells in dorsal midbrain of zebrafish larvae

Lin

Lee

2016

Sci Rep

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“…Another study reported 14-3-3 zeta binding to Cdc25B and inhibits its interaction with CyclinB/Cdk1 [14]. Cdc25 dual-specificity phosphatases are essential regulators that activate cyclin-dependent kinases(CDKs) at critical stages of the cell cycle, acting both in S phase and G2/M in mammalian cells [15]. Thus, developing selective inhibitors for Cdc25 family proteins could provided novel therapeutic strategies for cancer therapy [16–18].…”

Section: Discussionmentioning

confidence: 99%

Coexistence of YWHAZ amplification predicts better prognosis in muscle-invasive bladder cancer with CDKN2A or TP53 loss

Liu

Yang

et al. 2016

Oncotarget

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The amplification of YWHAZ was commonly seen in bladder cancer. We explore the biological significance of YWHAZ amplification on bladder cancer, and the correlation with important other molecular events. The Cancer Genome Atlas (TCGA) database was exploited to study the impact of YWHAZ amplification on either CDKN2A or TP53 mutations. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was also exploited to clustering of enriched genes in the cBioPortal Enrichment tests. There were 127 cases with available mutation and CNV data in the corresponding TCGA bladder cancer dataset, 20% of them had YWHAZ alteration. Patients with both YWHAZ amplification and CDKN2A loss demonstrated significantly better overall survival (OS) compared with CDKN2A loss alone. Patients with both YWHAZ amplification and TP53 mutation demonstrated significantly better overall survival (OS) and disease-free survival (DFS) compared with TP53 mutation alone. The amplification of YWHAZ, along with alteration of CDKN2A or TP53, predict better survival in bladder cancers that only had CDKN2A or TP53 alteration. The protective role of YWHAZ in bladder cancer deserve insightful further studies.

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“…Thus, elucidating molecular mechanisms underlying cell cycle checkpoints may provide new therapeutic targets for overcoming radioresistance. Cell division cycle 25 (CDC25) family phosphatases, consisting of CDC25A, B and C, play key roles in regulation of cell cycle progression under normal conditions and after DNA damage67. CDC25C has been extensively characterized in terms of function and regulation since its discovery as the first Cdc25 phosphatase.…”

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confidence: 99%

A signature motif in LIM proteins mediates binding to checkpoint proteins and increases tumour radiosensitivity

Zhang²,

Liang³

et al. 2017

Nat Commun

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Tumour radiotherapy resistance involves the cell cycle pathway. CDC25 phosphatases are key cell cycle regulators. However, how CDC25 activity is precisely controlled remains largely unknown. Here, we show that LIM domain-containing proteins, such as FHL1, increase inhibitory CDC25 phosphorylation by forming a complex with CHK2 and CDC25, and sequester CDC25 in the cytoplasm by forming another complex with 14-3-3 and CDC25, resulting in increased radioresistance in cancer cells. FHL1 expression, induced by ionizing irradiation in a SP1- and MLL1-dependent manner, positively correlates with radioresistance in cancer patients. We identify a cell-penetrating 11 amino-acid motif within LIM domains (eLIM) that is sufficient for binding CHK2 and CDC25, reducing the CHK2–CDC25 and CDC25–14-3-3 interaction and enhancing CDC25 activity and cancer radiosensitivity accompanied by mitotic catastrophe and apoptosis. Our results provide novel insight into molecular mechanisms underlying CDC25 activity regulation. LIM protein inhibition or use of eLIM may be new strategies for improving tumour radiosensitivity.

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Cdc25 and the importance of G₂control

Cited by 49 publications

References 49 publications

Stathmin-like 4 is critical for the maintenance of neural progenitor cells in dorsal midbrain of zebrafish larvae

Stathmin-like 4 is critical for the maintenance of neural progenitor cells in dorsal midbrain of zebrafish larvae

Coexistence of YWHAZ amplification predicts better prognosis in muscle-invasive bladder cancer with CDKN2A or TP53 loss

A signature motif in LIM proteins mediates binding to checkpoint proteins and increases tumour radiosensitivity

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Cdc25 and the importance of G2control

Cited by 49 publications

References 49 publications

Stathmin-like 4 is critical for the maintenance of neural progenitor cells in dorsal midbrain of zebrafish larvae

Stathmin-like 4 is critical for the maintenance of neural progenitor cells in dorsal midbrain of zebrafish larvae

Coexistence of YWHAZ amplification predicts better prognosis in muscle-invasive bladder cancer with CDKN2A or TP53 loss

A signature motif in LIM proteins mediates binding to checkpoint proteins and increases tumour radiosensitivity

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Cdc25 and the importance of G₂control