HIV-Tat promotes cellular proliferation and inhibits NGF-induced differentiation through mechanisms involving Id1 regulation

Bergonzini, Valeria; Delbue, Serena; Wang, Jin Ying; Reiss, Krzysztof; Prisco, Marco di; Amini, Shohreh; Khalili, Kamel; Peruzzi, Francesca

doi:10.1038/sj.onc.1207828

Cited by 19 publications

(20 citation statements)

References 64 publications

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“…Inhibition of Id-1 expression appears to be a common event following induction of cellular differentiation mediated by various factors (Norton et al, 1998; Zebedee and Hara, 2001; Ruzinova and Benezra, 2003; Bergonzini et al, 2004). However, less clear is the fact that down-regulation of Id-1 is preceded by its transient up-regulation (usually in the first 3 h of treatment).…”

Section: Resultsmentioning

confidence: 99%

Induction of Id-1 by FGF-2 involves activity of EGR-1 and sensitizes neuroblastoma cells to cell death

et al. 2011

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Inhibitor of differentiation-1 (Id-1) is a member of helix–loop–helix (HLH) family of proteins that regulate gene transcription through their inhibitory binding to basic-HLH transcription factors. Similarly to other members of this family, Id-1 is involved in the repression of cell differentiation and activation of cell growth. The dual function of Id-1, inhibition of differentiation, and stimulation of cell proliferation, might be interdependent, as cell differentiation is generally coupled with the exit from the cell cycle. Fibroblast growth factor-2 (FGF-2) has been reported to play multiple roles in different biological processes during development of the central nervous system (CNS). In addition, FGF-2 has been described to induce “neuronal-like” differentiation and trigger apoptosis in neuroblastoma SK-N-MC cells. Although regulation of Id-1 protein by several mitogenic factors is well-established, little is known about the role of FGF-2 in the regulation of Id-1. Using human neuroblastoma cell line, SK-N-MC, we found that treatment of these cells with FGF-2 resulted in early induction of both Id-1 mRNA and protein. The induction occurs within 1 h from FGF-2 treatment and is mediated by ERK1/2 pathway, which in turn stimulates expression of the early growth response-1 (Egr-1) transcription factor. We also demonstrate direct interaction of Egr-1 with Id-1 promoter in vitro and in cell culture. Finally, inhibition of Id-1 expression results in G2/M accumulation of FGF-2-treated cells and delayed cell death.

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Section: Resultsmentioning

confidence: 99%

Induction of Id-1 by FGF-2 involves activity of EGR-1 and sensitizes neuroblastoma cells to cell death

et al. 2011

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“…Shifting of the substrates along signaling pathways appears to be an interesting feature of Tat. For instance, we have previously shown the ability of Tat to promote the non-canonical activation of Stat5A in PC12 cells stimulated with NGF, which results in the inhibition of cellular differentiation [46]. Ultimately, since the activity of Tat on cellular processes appears to be cell-type specific, the end point of Tat/host interaction, including the Tat/SH3-client interaction, could be either inhibitory or stimulatory.…”

Section: Discussionmentioning

confidence: 99%

HIV-1 Tat binds to SH3 domains: Cellular and viral outcome of Tat/Grb2 interaction

Rom

Pacifici

Passiatore

et al. 2011

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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The Src-homology 3 (SH3) domain is one of the most frequent protein recognition modules (PRMs), being represented in signal transduction pathways and in several pathologies such as cancer and AIDS. Grb2 (growth factor receptor-bound protein 2) is an adaptor protein that contains two SH3 domains and is involved in receptor tyrosine kinase (RTK) signal transduction pathways. The HIV-1 transactivator factor Tat is required for viral replication and it has been shown to bind directly or indirectly to several host proteins, deregulating their functions. In this study, we show interaction between the cellular factor Grb2 and the HIV-1 trans-activating protein Tat. The binding is mediated by the proline-rich sequence of Tat and the SH3 domain of Grb2. As the adaptor protein Grb2 participates in a wide variety of signaling pathways, we characterized at least one of the possible downstream effects of the Tat/Grb2 interaction on the well-known IGF-1R/Raf/MAPK cascade. We show that the binding of Tat to Grb2 impairs activation of the Raf/MAPK pathway, while potentiating the PKA/Raf inhibitory pathway. The Tat/Grb2 interaction affects also viral function by inhibiting the Tat-mediated transactivation of HIV-1 LTR and viral replication in infected primary microglia.

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“…The ability of HIV-1 Tat to be secreted by HIVinfected cells and to freely enter neighboring noninfected cells, including neurons, suggests a critical role for this viral protein in mediating neuronal damage. Considering that Tat can bind tubulin polymers (Chen et al, 2002) and block cellular differentiation and neurite outgrowth (Mondal and Agrawal, 1996;Bergonzini et al, 2004), we asked whether Tat-mediated neurotoxicity depends on its interaction with microtubules, which are the major structural and functional component of neuronal processes. Here, we used a model of rat primary neurons to investigate the effects of Tat in two different stages of neuronal maturation: an early stage in which the cells start to extend the neurites and a later stage in which neuronal processes are fully extended.…”

Section: Discussionmentioning

confidence: 99%

“…The viral regulatory protein Tat is among the critical factors that are believed to be involved in the onset and progression of autoimmunodeficiency syndrome (AIDS) and AIDS-associated neurological complications (Kaul et al, 2001;Nath, 2002;Peruzzi et al, 2005;Peruzzi, 2006). An intriguing aspect of Tat-induced neurotoxicity includes impairment of synaptic plasticity (Perry et al, 2005) and inhibition of neurite outgrowth (Bergonzini et al, 2004). Both extension and maintenance of neuronal processes are governed by the structural and functional integrity of the cytoskeleton.…”

Section: Introductionmentioning

confidence: 99%

Tubulin-Mediated Binding of Human Immunodeficiency Virus-1 Tat to the Cytoskeleton Causes Proteasomal-Dependent Degradation of Microtubule-Associated Protein 2 and Neuronal Damage

Aprea

Valle²,

Mameli³

et al. 2006

J. Neurosci.

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One of the hallmarks of human immunodeficiency virus (HIV)-1 associated pathology in the CNS is deterioration of neuronal processes.Although there is mounting evidence of neuronal toxicity and cell death induced by the HIV-1 transactivating factor Tat, the molecular events linked directly to its detrimental effect on neuronal cells remain unclear. In this study, we used rat embryonic cortical neurons and demonstrated that Tat causes rapid degradation of microtubule-associated protein 2 (MAP2) and the collapse of cytoskeletal filaments. The mechanism of Tat action on MAP2 stability involved Tat

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HIV-Tat promotes cellular proliferation and inhibits NGF-induced differentiation through mechanisms involving Id1 regulation

Cited by 19 publications

References 64 publications

Induction of Id-1 by FGF-2 involves activity of EGR-1 and sensitizes neuroblastoma cells to cell death

Induction of Id-1 by FGF-2 involves activity of EGR-1 and sensitizes neuroblastoma cells to cell death

HIV-1 Tat binds to SH3 domains: Cellular and viral outcome of Tat/Grb2 interaction

Tubulin-Mediated Binding of Human Immunodeficiency Virus-1 Tat to the Cytoskeleton Causes Proteasomal-Dependent Degradation of Microtubule-Associated Protein 2 and Neuronal Damage

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