A novel CyclinE/CyclinA-CDK Inhibitor targets p27Kip1 degradation, cell cycle progression and cell survival: Implications in cancer therapy

Dai, Lu; Liu, Yuqing; Liu, Junyang; Wen, Xiaoming; Xu, Zhengshuang; Wang, Zhuo; Sun, Hong; Tang, Shoubin; Maguire, Anita R.; Quan, Jing; Zhang, Hui; Ye, Tao

doi:10.1016/j.canlet.2013.01.025

Cited by 46 publications

(34 citation statements)

References 32 publications

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“…Cyclin A-CDK2 promotes S-phase progression by either directly phosphorylating substrates such as Cdh1, Rb, p21 and p27 or indirectly by phosphorylating substrates that are able to regulate these factors. [44][45][46][47] It is tempting to speculate that TBX3 may be an example of the latter to ensure repression of p21. This would be important to ensure a negative feedback loop because p21 can inhibit cyclin A-CDK2 activity.…”

Section: Discussionmentioning

confidence: 99%

The T-Box factor TBX3 is important in S-phase and is regulated by c-Myc and cyclin A-CDK2

et al. 2015

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The transcription factor, TBX3, is critical for the formation of, among other structures, the heart, limbs and mammary glands and haploinsufficiency of the human TBX3 gene result in ulnar-mammary syndrome which is characterized by hypoplasia of these structures. On the other hand, the overexpression of TBX3 is a feature of a wide range of cancers and it has been implicated in several aspects of the oncogenic process. This includes its ability to function as an immortalizing gene and to promote proliferation through actively repressing negative cell cycle regulators. Together this suggests that TBX3 levels may need to be tightly regulated during the cell cycle. Here we demonstrate that this is indeed the case and that TBX3 mRNA and protein levels peak at S-phase and that the TBX3 protein is predominantly localized to the nucleus of S-phase cells. The increased levels of TBX3 in S-phase are shown to occur transcriptionally through activation by c-Myc at E-box motifs located at ¡1210 and ¡701 bps and post-translationally by cyclin A-CDK2 phosphorylation. Importantly, when TBX3 is depleted by shRNA the cells accumulate in S-phase. These results suggest that TBX3 is required for cells to transit through S-phase and that this function may be linked to its role as a proproliferative factor.

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Section: Discussionmentioning

confidence: 99%

The T-Box factor TBX3 is important in S-phase and is regulated by c-Myc and cyclin A-CDK2

et al. 2015

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“…35,36) The progression of mitosis is controlled by cyclins, a family of proteins activating CDKs. 37) Cyclin A1 (CCNA1) and CCNA2 complex and CDK2 are essential for mitosis. 38,39) Additionally, cell-division cycle protein 20 (CDC20) regulates mitotic exit by targeting cyclins A and B.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Gene Expression During the Development of Congestive Heart Failure After Myocardial Infarction in Rat Models

Zhang

et al. 2015

Int. Heart J.

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SummaryOur study aimed to investigate the gene expression at different myocardial infarction (MI) phases and to understand the development mechanisms of congestive heart failure (CHF) after MI. Dataset GSE1957 including 24 samples of rat left ventricles at 1-day post MI or sham operation and 7-day post MI or sham operation was downloaded from Gene Expression Ominibus. The data were normalized with an affyPLM package and differentially expressed genes (DEGs) were identified with a Linear Models for Microarray Data package. Heat maps of the DEGs were constructed using Cluster 3.0. GO (Gene Ontology) enrichment analysis of the DEGs was performed in Database for Annotation, Visualization, and Integrated Discovery. A protein-protein interaction (PPI) network was constructed by Biomolecular Interaction Network Database and visualized by Cytoscape, and a subnetwork was analyzed using plugin ClusterONE in Cytoscape. A total of 5 DEGs at 1-day post-MI, 5 DEGs at 7-day post-MI, and 7 DEGs between the MI and sham groups at 1-day and 7-day post-MI were identified. For the GO category analysis, DEGs at 1-day post-MI were enriched in response to cytokine stimulus. DEGs at 7-day post-MI were enriched in response to inorganic substance and chemical homeostasis. DEGs between 1-day and 7-day post-MI including CDK2 and CDC20 were significantly enriched in mitosis. CDK2, ANXA1, CDC20, and AQP2 were included in the PPI network, and CDK2 was the only DEG included in the subnetwork. In conclusion, the induction of DEGs at 7-day post-MI might participate in the response to a hormone and endogenous stimulus to regulate the development of CHF after MI. (Int Heart J 2015; 56: 444-449) Key words: Differentially expressed gene, Interaction network, CDK2, AQP2 M yocardial infarction (MI) is commonly known as heart attack. MI is a leading cause of heart failure and one of the major causes of the death and disability, and is a chronic disease and can even go undetected, eventually leading to a sudden death.1,2) Patients with MI sometimes have chest pain while 64% of the cases may not even have any symptoms.3) Therefore, an urgent task is to develop diagnostic and therapeutic methods for MI.In recent years, studies on genes have provided us with information for disease diagnosis and therapy due to their high sensitivity, specificity, and fast speed. The relation between gene expression and MI has been studied extensively, and the progression of congestive heart failure (CHF) after MI is complex and related to several changes. [4][5][6][7] For example, the variants of gene ALOX5AP which encodes 5-lipoxygenase activating protein are associated with the pathogenesis of MI by increasing leukotriene production and inflammation. 4) Andersson, et al reported that the expression of 10 neuronal type regulated genes including muscarinic m4, ATP receptor P2rx4, nerve growth factor receptor, and cardiac Kcne1 were all increased in 7-day post-MI CHF hearts, while fewer genes were differentially expressed at 1-day post MI. 6) However, the underlying funct...

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“…Inactivation of Skp2 by stable complex formation was also seen for p27 Kip1 inactivation of cyclin A-cdk2 (Galea et al, 2008; Dai et al, 2013). Evidence that a complex between MAGE-A11 and Skp2 inhibits the self-ubiquitination of Skp2 suggests that MAGE-A11 can regulate Skp2-mediated ubiquitin ligase activity.…”

Section: 0 Discussionmentioning

confidence: 82%

Melanoma antigen-A11 regulates substrate-specificity of Skp2-mediated protein degradation

Chen

Geng

et al. 2017

Molecular and Cellular Endocrinology

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Melanoma antigen-A11 (MAGE-A11) is a proto-oncogene involved in androgen receptor signaling and androgen-dependent cell growth. In this report we provide evidence that MAGE-A11 interacts with Skp2 (S phase kinase-associated protein), the substrate recognition protein of the Skp1-Cullin1-F-box E3 ubiquitin ligase, and with Skp2 binding protein, cyclin A. A similar cyclin A binding motif in MAGE-A11 and Skp2 was consistent with a competitive relationship between MAGE-A11 and Skp2 in binding cyclin A. Skp2 inhibited MAGE-A11 interaction with cyclin A. Differential effects of MAGE-A11 on Skp2-mediated protein degradation were also revealed. MAGE-A11 increased Skp2-mediated degradation of cyclin A and retinoblastoma-related protein p130. In contrast, MAGE-A11 decreased Skp2-mediated degradation of E2F1 and Skp2 self-ubiquitination. Stabilization of E2F1 by MAGE-A11 was associated with sequestration and inactivation of Skp2 through the formation of an E2F1-MAGE-A11-Skp2 complex. We conclude that direct interactions of MAGE-A11 with Skp2 and cyclin A regulate the substrate-specificity of Skp2-mediated protein degradation.

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A novel CyclinE/CyclinA-CDK Inhibitor targets p27Kip1 degradation, cell cycle progression and cell survival: Implications in cancer therapy

Cited by 46 publications

References 32 publications

The T-Box factor TBX3 is important in S-phase and is regulated by c-Myc and cyclin A-CDK2

The T-Box factor TBX3 is important in S-phase and is regulated by c-Myc and cyclin A-CDK2

Analysis of Gene Expression During the Development of Congestive Heart Failure After Myocardial Infarction in Rat Models

Melanoma antigen-A11 regulates substrate-specificity of Skp2-mediated protein degradation

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