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192 results on '"Bottero, Virginie"'

11. Phosphorylation of p53 by I[kappa]B kinase 2 promotes its degradation by [beta]-TrCP

Author

Xia, Yifeng, Padre, Roanna C., De Mendoza, Tatiana Hurtado, Bottero, Virginie, Tergaonkar, Vinay B., and Verma, Inder M.

Subjects
Cancer cells -- Health aspects, Cancer cells -- Research, DNA damage -- Causes of, DNA damage -- Physiological aspects, DNA damage -- Research, Phosphorylation -- Research, Science and technology
Abstract

Functional inactivation of p53 and constitutive activation of the NF-[kappa]B pathway has been associated with several human cancers. In this study, we show that I[kappa]B kinase 2 (IKK2/IKK[beta]), which is critical for NF-[kappa]B activation, also phosphorylates p53. Phosphorylation of p53 at serines 362 and 366 by IKK2 leads to its recruitment to and ubiquitination by [beta]-TrCP1. Degradation of ubiquitinated p53 is independent of Mdm2, because it occurs in both wild-type and [Mdm2.sup.-/-] cells. SiRNA-mediated reduction in the levels of [beta]-TrCP1 and other members of the [SCF.sup.[beta]]-TrCP1]E3 ubiquitin ligase complex or overexpression of a dominant negative form of [beta]-TrCP1 enhances p53 stability. Substitutions at Ser-362 and 366 of p53 by alanines (p53 AA) result in reduced phosphorylation of p53 by IKK2, decreased association with [beta]-TrCP1, and thus increased stability of p53 and expression of p53 target genes such as p21, altering the G1 phase of the cell cycle. Our results identify IKK2 and [beta]-TrCP1 as novel regulators of the p53 pathway and suggest that blocking of IKK2 and [beta]-TrCP1 could be a means of regulating p53 stability and thereby modulating its biological activity. [beta]-TrCP1 | DNA damage | IKK2 | p53 stability

Published
2009

13. Enhanced NF-[kappa]B activation and cellular function in macrophages lacking l[kappa]B kinase 1 (IKK1)

Author

Li, Qiutang, Lu, Qingxian, Bottero, Virginie, Estepa, Gabriela, Morrison, Lisa, Mercurio, Frank, and Verma, Inder M.

Subjects
Autoimmunity -- Research, Macrophages -- Research, Protein kinases -- Research, Science and technology
Abstract

I[kappa]B kinase (IKK) complex plays a key regulatory role in macrophages for NF-[kappa]B activation during both innate and adaptive immune responses. Because [IKK1.sup.-/-] mice died at birth, we differentiated functional macrophages from embryonic day 15.5 IKK1 mutant embryonic liver. The embryonic liver-derived macrophage (ELDM) showed enhanced phagocytotic clearance of bacteria, more efficient antigen-presenting capacity, elevated secretion of several key proinflammatory cytokines and chemokines, and known NF[kappa]B target genes. Increased NF[kappa]B activity in IKK1 mutant ELDM was the result of prolonged degradation of I[kappa]B[alpha] in response to infectious pathogens. The delayed restoration of I[kappa]B[alpha] in pathogen-activated [IKK1.sup.-/-] ELDM was a direct consequence of uncontrolled IKK2 kinase activity. We hypothesize that IKK1 plays a checkpoint role in the proper control of IKBa kinase activity in innate and adaptive immunity. I[kappa]B[alpha] | LPS

Published
2005

15. Activation of transcription factor NF-κB requires ELKS, an IκB kinase regulatory subunit

Author

Sigala, Jeanette L. Ducut, Bottero, Virginie, Young, David B., Shevchenko, Andrej, Mercurio, Frank, and Verma, Inder M.

Subjects
Protein kinases -- Research -- Properties, Genetic transcription -- Research -- Properties, Science and technology, Research, Properties
Abstract

The nuclear factor--kappa B (NF-κB) family of transcription factors plays a seminal role in inflammation, apoptosis, development, and cancer. Modulation of NF-κB--mediated gene expression in response to diverse signals is coordinated by the IκB kinase (IKK) complex. We identified ELKS, an essential regulatory subunit of the IKK complex. Silencing ELKS expression by RNA interference blocked induced expression of NF-κB target genes, including the NF-κB inhibitor IκBα and proinflammatory genes such as cyclo-oxygenase 2 and interleukin 8. These cells were also not protected from apoptosis in response to cytokines. ELKS likely functions by recruiting IκBα to the IKK complex and thus serves a regulatory function for IKK activation., The transcription factor NF-κB coordinates inducible gone expression in many cell types during fundamental biological processes, including the immune response, apoptosis, oncogenesis, and development (1, 2). Exposure of cells to [...]

Published
2004

36. Gene therapy: Is IL2RG oncogenic in T-cell development?: X-SCID transgene leukaemogenicity (reply)

Author

Woods, Niels-Bjarne, Bottero, Virginie, Schmidt, Manfred, von Kalle, Christof, and Verma, Inder M.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Niels-Bjarne Woods [1]; Virginie Bottero [1]; Manfred Schmidt [2]; Christof von Kalle [2]; Inder M. Verma [1] Using a lentiviral vector and a murine model of X-linked severe combined [...]

Published
2006
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44. NF-kappaB modulation and ionizing radiation: mechanisms and future directions for cancer treatment.

Author

Magné, N, Toillon, Robert-Alain, Bottero, Virginie, Didelot, Céline, Van Houtte, Paul, Gérard, Jean-Pierre, Peyron, Jean François, Magné, N, Toillon, Robert-Alain, Bottero, Virginie, Didelot, Céline, Van Houtte, Paul, Gérard, Jean-Pierre, and Peyron, Jean François

Abstract

NF-kappaB transcription factor regulates important cellular processes ranging from establishment of the immune and inflammatory responses to regulation of cell proliferation or apoptosis, through the induction of a large array of target genes. NF-kappaB is now considered as an important actor in the tumorigenic process mainly because it exerts strong anti-apoptotic functions in cancer cells. NF-kappaB is triggered by chimio- and radio-therapeutic strategies that are intended to eliminate cancerous cells through induction of apoptosis. Numerous studies have demonstrated that inhibition of NF-kappaB by different means increased sensitivity of cancer cells to the apoptotic action of diverses effectors such as TNFalpha or chemo- or radio-therapies. From these studies as emerged the concept that NF-kappaB blockade could be associated to conventional therapies in order to increase their efficiency. This review focuses on the current knowledge on NF-kappaB regulation and discusses the therapeutic potential of targeting NF-kappaB in cancer in particular during radiotherapy., Journal Article, Review, SCOPUS: sh.j, info:eu-repo/semantics/published

Published
2006

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