Complementation of human papillomavirus type 16 E6 and E7 by Jagged1-specific Notch1-phosphatidylinositol 3-kinase signaling involves pleiotropic oncogenic functions independent of CBF1;Su(H);Lag-1 activation.
We have analyzed the induction and role of phosphatidylinositol 3-kinase (PI3K) by Notch signaling in human papillomavirus (HPV)-derived cancers. Jagged1, in contrast to Delta1, is preferentially upregulated in human cervical tumors. Jagged1 and not Delta1 expression sustained in vivo tumors by HPV16 oncogenes in HaCaT cells. Further, Jagged1 expression correlates with the rapid induction of PI3K-mediated epithelial-mesenchymal transition in both HaCaT cells and a human cervical tumor-derived cell line, suggestive of Delta1;Serrate/Jagged;Lag2 ligand-specific roles. Microarray analysis and dominant-negatives reveal that Notch-PI3K oncogenic functions can be independent of CBF1;Su(H);Lag-1 activation and instead relies on Deltex1, an alternative Notch effector.
Veeraraghavalu
Karthikeyan
K
National Centre for Biological Sciences, TIFR, UAS-GKVK Campus, Bangalore 560065, India.
Subbaiah
Vanitha K
VK
Srivastava
Sweta
S
Chakrabarti
Oishee
O
Syal
Ruchi
R
Krishna
Sudhir
S
D002135:Calcium-Binding Proteins; D002294:Carcinoma, Squamous Cell / Q000503:physiopathology; D002460:Cell Line; D045744:Cell Line, Tumor; D054407:Chemokine CCL4; D019742:Chemokines, CC; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D027383:Papillomaviridae / Q000472:pathogenicity; D050725:Papillomavirus E7 Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018121:Receptors, Cytokine / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000503:physiopathology; D002578:Uterine Cervical Dysplasia / Q000503:physiopathology
C066507:CCL4 protein, human; C498762:CRLF2 protein, human; D002135:Calcium-Binding Proteins; D054407:Chemokine CCL4; D019742:Chemokines, CC; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D019402:Macrophage Inflammatory Proteins; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C497570:RBPJ protein, human; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D012097:Repressor Proteins; D000072099:Serrate-Jagged Proteins; D014157:Transcription Factors; C059731:oncogene protein E7, Human papillomavirus type 16; D019869:Phosphatidylinositol 3-Kinases