Proteomic patterns of cervical cancer cell lines, a network perspective

Higareda‐Almaraz, Juan Carlos; Enríquez-Gasca, María del Rocío; Hernández‐Ortíz, Magdalena; Resendis‐Antonio, Osbaldo; Encarnación‐Guevara, Sergio

doi:10.1186/1752-0509-5-96

Cited by 55 publications

(46 citation statements)

References 78 publications

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“…Gels were dyed in colloidal Coomassie [84] and scanned in a GS-800 densitometer (Bio-Rad Laboratories, CA). Digital images were analyzed and compared using the PDQuest 8.0.1 software from the same company.…”

Section: Methodsmentioning

confidence: 99%

New insights into Escherichia coli metabolism: carbon scavenging, acetate metabolism and carbon recycling responses during growth on glycerol

et al. 2012

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BackgroundGlycerol has enhanced its biotechnological importance since it is a byproduct of biodiesel synthesis. A study of Escherichia coli physiology during growth on glycerol was performed combining transcriptional-proteomic analysis as well as kinetic and stoichiometric evaluations in the strain JM101 and certain derivatives with important inactivated genes.ResultsTranscriptional and proteomic analysis of metabolic central genes of strain JM101 growing on glycerol, revealed important changes not only in the synthesis of MglB, LamB and MalE proteins, but also in the overexpression of carbon scavenging genes: lamB, malE, mglB, mglC, galP and glk and some members of the RpoS regulon (pfkA, pfkB, fbaA, fbaB, pgi, poxB, acs, actP and acnA). Inactivation of rpoS had an important effect on stoichiometric parameters and growth adaptation on glycerol. The observed overexpression of poxB, pta, acs genes, glyoxylate shunt genes (aceA, aceB, glcB and glcC) and actP, suggested a possible carbon flux deviation into the PoxB, Acs and glyoxylate shunt. In this scenario acetate synthesized from pyruvate with PoxB was apparently reutilized via Acs and the glyoxylate shunt enzymes. In agreement, no acetate was detected when growing on glycerol, this strain was also capable of glycerol and acetate coutilization when growing in mineral media and derivatives carrying inactivated poxB or pckA genes, accumulated acetate. Tryptophanase A (TnaA) was synthesized at high levels and indole was produced by this enzyme, in strain JM101 growing on glycerol. Additionally, in the isogenic derivative with the inactivated tnaA gene, no indole was detected and acetate and lactate were accumulated. A high efficiency aromatic compounds production capability was detected in JM101 carrying pJLBaroGfbrtktA, when growing on glycerol, as compared to glucose.ConclusionsThe overexpression of several carbon scavenging, acetate metabolism genes and the absence of acetate accumulation occurred in JM101 cultures growing on glycerol. To explain these results it is proposed that in addition to the glycolytic metabolism, a gluconeogenic carbon recycling process that involves acetate is occurring simultaneously in this strain when growing on glycerol. Carbon flux from glycerol can be efficiently redirected in JM101 strain into the aromatic pathway using appropriate tools.

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Section: Methodsmentioning

confidence: 99%

New insights into Escherichia coli metabolism: carbon scavenging, acetate metabolism and carbon recycling responses during growth on glycerol

et al. 2012

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“…In the case of 14-3-3, the protein has been reported to be overexpressed in a variety of human cancers (35,36,42,43), including cervical cancer (44), and the ablation of 14-3-3 expression in such cells has been proposed as a potential therapeutic option for some tumor types (32,43). While the modes of action of 14-3-3 are diverse and affect multiple signaling pathways, a common theme is the ability to recognize phosphorylated substrates and thereby directly modulate their respective modes of action.…”

Section: Discussionmentioning

confidence: 99%

High-Risk Human Papillomavirus E6 Oncoproteins Interact with 14-3-3ζ in a PDZ Binding Motif-Dependent Manner

Boon

Banks

2013

J Virol

110

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Cervical cancer develops through the combined activities of the human papillomavirus (HPV) E6 and E7 oncoproteins. A defining characteristic of E6 oncoproteins derived from cancer-causing HPV types is the presence of a PDZ binding motif (PBM) at the extreme carboxy terminus of the protein which is absent from E6 proteins derived from the so-called low-risk HPV types. Within this PBM is also a protein kinase A (PKA) phospho-acceptor site, which is thought to negatively regulate the association of E6 with its PDZ domain-containing substrates. We can now show that phosphorylation of E6 by PKA and/or AKT confers the ability to interact with 14-3-3. The interaction is direct and specific for the high-risk HPV E6 oncoproteins, although there are significant differences in the efficiencies with which HPV-16, HPV-18, and HPV-31 E6 oncoproteins can associate with 14-3-3; this correlates directly with their respective susceptibilities to phosphorylation by PKA and/or AKT. We demonstrate here that the interaction between E6 and 14-3-3 also requires integrity of the E6 PBM, and downregulation of 14-3-3 results in a marked reduction in the levels of HPV-18 E6 expression in HeLa cells. Using phospho-specific anti-E6 antibodies, we also demonstrate significant levels of E6 phosphorylation in vivo. These studies redefine the potential relevance of the E6 PBM in the development of cervical cancer, suggesting that interaction with 14-3-3, as well as the more well-established interactions with PDZ domaincontaining substrates, is likely to be responsible for the biological activities attributed to this region of the high-risk HPV E6 oncoproteins.H uman papillomaviruses (HPVs) are the causative agents of a large number of different human cancers, including cervical cancer, other anogenital cancers, and a growing number of head and neck cancers (reviewed in reference 1). Of these, cervical cancer is by far the most prevalent, being the second major cause of cancer-related death for women worldwide. Recently, the WHO classified 12 different cervical cancer-causing HPV types, with HPV-16 and HPV-18 being predominant (2). A defining feature of cervical cancers and derived cell lines is the continued expression of two viral oncoproteins, E6 and E7, many years after the initial immortalizing events (3-5). Indeed, abrogation of their respective functions or expression results in a cessation of cell growth and induction of senescence and/or apoptosis (6-8). Therefore, these two proteins represent ideal targets for potential therapeutic intervention in HPV-induced malignancies.The HPV E6 and E7 proteins contribute to tumor development by directly interfering with critical growth-regulatory pathways (9, 10). The so-called high-risk cancer-causing HPV E7 oncoproteins interact with a very large number of cellular proteins, many of which are involved in the regulation of cell proliferation and control of the cell cycle, as well as gene expression and DNA damage response pathways. These include the pRb family of tumor suppressor proteins (reviewe...

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“…While this problem can exist with any pathway analysis, Gene Ontology (GO) annotations are particularly susceptible due to the database’s large, hierarchical structure [27]. Some studies have restricted analysis of GO terms to certain levels in the hierarchy [13, 28], while a new Bayesian method incorporates the structure of the hierarchy as prior information into its pathway association metric [29]. However, users of these approaches should be aware that the information content at particular GO levels is unpredictable [30].…”

Section: Preparing Data For Association Testingmentioning

confidence: 99%

Pathway analysis of genomic data: concepts, methods, and prospects for future development

et al. 2012

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Genome-wide data sets are increasingly being used to identify biological pathways and networks underlying complex diseases. In particular, analyzing genomic data through sets defined by functional pathways offers the potential of greater power for discovery and natural connections to biological mechanisms. With the burgeoning availability of next-generation sequencing, this is an opportune moment to revisit strategies for pathway-based analysis of genomic data. Here, we synthesize relevant concepts and extant methodologies to guide investigators in study design and execution. We also highlight ongoing challenges and proposed solutions. As relevant analytical strategies mature, pathways and networks will be ideally placed to integrate data from diverse -omics sources in order to harness the extensive, rich information related to disease and treatment mechanisms.

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Proteomic patterns of cervical cancer cell lines, a network perspective

Cited by 55 publications

References 78 publications

New insights into Escherichia coli metabolism: carbon scavenging, acetate metabolism and carbon recycling responses during growth on glycerol

New insights into Escherichia coli metabolism: carbon scavenging, acetate metabolism and carbon recycling responses during growth on glycerol

High-Risk Human Papillomavirus E6 Oncoproteins Interact with 14-3-3ζ in a PDZ Binding Motif-Dependent Manner

Pathway analysis of genomic data: concepts, methods, and prospects for future development

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