Phosphorylation of the ErbB3 binding protein Ebp1 by p21-activated kinase 1 in breast cancer cells

Akinmade, Damilola; Talukder, Amjad H.; Zhang, Y.; Luo, Wei; Kumar, Rakesh; Hamburger, Anne W.

doi:10.1038/sj.bjc.6604261

Cited by 22 publications

(35 citation statements)

References 39 publications

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“…The constitutive activation of PAK-1 rapidly induced breast cancer cell proliferation, and mutant kinase active T423E PAK-1 transgenic mice were found to develop hyperplasia in the mammary epithelium (Akinmade et al, 2008). This hyperplasia was shown to respond to estrogen receptor activation, consistent with widely upregulated PAK-1 levels detected in human breast cancers (Akinmade et al, 2008). Furthermore, PAK-1 was also shown to stimulate the expression of the Wnt target gene, cyclin D1 (He et al, 2008).…”

Section: Discussionmentioning

confidence: 66%

“…PAK-1 is overexpressed in hepatocellular carcinoma, especially in the more aggressive types, and has a role in enhancing metastasis (Ching et al, 2007). The constitutive activation of PAK-1 rapidly induced breast cancer cell proliferation, and mutant kinase active T423E PAK-1 transgenic mice were found to develop hyperplasia in the mammary epithelium (Akinmade et al, 2008). This hyperplasia was shown to respond to estrogen receptor activation, consistent with widely upregulated PAK-1 levels detected in human breast cancers (Akinmade et al, 2008).…”

Section: Discussionmentioning

confidence: 66%

“…The serine/threonine kinase P-21-activated protein kinase-1 (PAK-1) is known to be involved in the development and metastasis of tumors from various tissues, including the intestine (Carter et al, 2004;Ching et al, 2007;Akinmade et al, 2008). PAK-1 was initially recognized as a downstream target of the Rho family GTPases, Rac1 and Cdc42, in regulating actin remodeling (Knaus and Bokoch, 1998;Zhou and Field, 2004;Arias-Romero and Chernoff, 2008).…”

Section: Introductionmentioning

confidence: 99%

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P-21-activated protein kinase-1 functions as a linker between insulin and Wnt signaling pathways in the intestine

et al. 2009

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Hyperinsulinemia and type II diabetes are associated with an increased risk of developing colorectal tumors. We found previously that in intestinal cells, insulin or insulinlike growth factor-1 stimulates c-Myc and cyclin D1 protein expression through both Akt-dependent and Aktindependent mechanisms. The effect of Akt is attributed to the stimulation of c-Myc translation by mammalian target of rapamycin. However, Akt-independent stimulation was, associated with an increase in b-catenin (b-cat) in the nucleus and an increased association between b-cat and T-cell factor binding sites on the c-Myc promoter, detected by chromatin immunoprecipitation. In this study, we show that insulin stimulated the phosphorylation/ activation of p-21-activated protein kinase-1 (PAK-1) in an Akt-independent manner in vitro and in an in vivo hyperinsulinemic mouse model. Significantly, shRNA (small hairpin RNA)-mediated PAK-1 knockdown attenuated both basal and insulin-stimulated c-Myc and cyclin D1 expression, associated with a marked reduction in extracellular signal-regulated kinase activation and b-cat phosphorylation at Ser675. Furthermore, PAK-1 silencing led to a complete blockade of insulin-stimulated b-cat binding to the c-Myc promoter and cellular growth. Finally, inhibition of MEK, a downstream target of PAK-1, blocked insulin-stimulated nuclear b-cat accumulation and c-Myc expression. Our observations suggest that PAK-1 serves as an important linker between insulin and Wnt signaling pathways.

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

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P-21-activated protein kinase-1 functions as a linker between insulin and Wnt signaling pathways in the intestine

et al. 2009

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“…When FBP1 in the cell became saturated with added p53, the heat signal diminished. The absorbed heat was measured to determine the binding constant (K) or dissociation constant (37) of interaction between FBP1 and p53 (Fig. 3D).…”

Section: Fbp1 Is Expressed In Hcc Tumors With a History Of Chronic Hementioning

confidence: 99%

FUSE Binding Protein 1 Facilitates Persistent Hepatitis C Virus Replication in Hepatoma Cells by Regulating Tumor Suppressor p53

Dixit

Pandey

Liu

et al. 2015

J Virol

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Hepatitis C virus (HCV) is a leading cause of chronic hepatitis C (CHC), liver cirrhosis, and hepatocellular carcinoma (HCC).Immunohistochemistry of archived HCC tumors showed abundant FBP1 expression in HCC tumors with the CHC background. Oncomine data analysis of normal versus HCC tumors with the CHC background indicated a 4-fold increase in FBP1 expression with a concomitant 2.5-fold decrease in the expression of p53. We found that FBP1 promotes HCV replication by inhibiting p53 and regulating BCCIP and TCTP, which are positive and negative regulators of p53, respectively. The severe inhibition of HCV replication in FBP1-knockdown Huh7.5 cells was restored to a normal level by downregulation of either p53 or BCCIP. Although p53 in Huh7.5 cells is transcriptionally inactive as a result of Y220C mutation, we found that the activation and DNA binding ability of Y220C p53 were strongly suppressed by FBP1 but significantly activated upon knockdown of FBP1. Transient expression of FBP1 in FBP1 knockdown cells fully restored the control phenotype in which the DNA binding ability of p53 was strongly suppressed. Using electrophoretic mobility shift assay (EMSA) and isothermal titration calorimetry (ITC), we found no significant difference in in vitro target DNA binding affinity of recombinant wild-type p53 and its Y220C mutant p53. However, in the presence of recombinant FBP1, the DNA binding ability of p53 is strongly inhibited. We confirmed that FBP1 downregulates BCCIP, p21, and p53 and upregulates TCTP under radiation-induced stress. Since FBP1 is overexpressed in most HCC tumors with an HCV background, it may have a role in promoting persistent virus infection and tumorigenesis. IMPORTANCEIt is our novel finding that FUSE binding protein 1 (FBP1) strongly inhibits the function of tumor suppressor p53 and is an essential host cell factor required for HCV replication. Oncomine data analysis of a large number of samples has revealed that overexpression of FBP1 in most HCC tumors with chronic hepatitis C is significantly linked with the decreased expression level of p53. The most significant finding is that FBP1 not only physically interacts with p53 and interferes with its binding to the target DNA but also functions as a negative regulator of p53 under cellular stress. FBP1 is barely detectable in normal differentiated cells; its overexpression in HCC tumors with the CHC background suggests that FBP1 has an important role in promoting HCV infection and HCC tumors by suppressing p53. H epatitis C virus (HCV) infection is a leading cause of chronic liver diseases. More than a decade after the identification of HCV as the major causative agent of non-A, non-B hepatitis (1), molecular strategies for complete eradication of HCV infection are actively pursued. HCV is the major cause of chronic liver disease. According to new findings from the U.S. Centers for Disease Control and Prevention (CDC), the number of individuals in the U.S. living with chronic hepatitis C virus infection is about 2.7 million (2). Globa...

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“…[39]. The EBP1 has been shown to be a transcriptional corepressor that inhibits the growth of human breast cancer cell lines [53].…”

Section: Leukemiamentioning

confidence: 99%

Feature Selection for Microarray Gene Expression Data Using Simulated Annealing Guided by the Multivariate Joint Entropy

González-Navarro

Belanche-Muñoz

2014

CyS

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Abstract-In this work a new way to calculate the multivariate joint entropy is presented. This measure is the basis for a fast information-theoretic based evaluation of gene relevance in a Microarray Gene Expression data context. Its low complexity is based on the reuse of previous computations to calculate current feature relevance.The µ-TAFS algorithm -named as such to differentiate it from previous TAFS algorithms-implements a simulated annealing technique specially designed for feature subset selection. The algorithm is applied to the maximization of gene subset relevance in several public-domain microarray data sets. The experimental results show a notoriously high classification performance and low size subsets formed by biologically meaningful genes.

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Phosphorylation of the ErbB3 binding protein Ebp1 by p21-activated kinase 1 in breast cancer cells

Cited by 22 publications

References 39 publications

P-21-activated protein kinase-1 functions as a linker between insulin and Wnt signaling pathways in the intestine

P-21-activated protein kinase-1 functions as a linker between insulin and Wnt signaling pathways in the intestine

FUSE Binding Protein 1 Facilitates Persistent Hepatitis C Virus Replication in Hepatoma Cells by Regulating Tumor Suppressor p53

Feature Selection for Microarray Gene Expression Data Using Simulated Annealing Guided by the Multivariate Joint Entropy

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