𝔖 Bobbio Scriptorium
✦   LIBER   ✦

Dysregulation of NGF-signaling and Egr-1 expression by Tat in neuronal cell culture

✍ Scribed by Nune Darbinian-Sarkissian; Marta Czernik; Francesca Peruzzi; Jennifer Gordon; Jay Rappaport; Krzysztof Reiss; Kamel Khalili; Shohreh Amini

Publisher
John Wiley and Sons
Year
2006
Tongue
English
Weight
413 KB
Volume
208
Category
Article
ISSN
0021-9541

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

Examination of signal transduction pathways that modulate neuronal cell differentiation and protection against apoptosis has revealed a central role for the MAPK/Erk cascade. The activation of MAPK/Erk through the TrkA NGF signaling pathway is critical for growth and survival of neuronal cells. Here, we investigate the impact of HIV‐1 Tat on the NGF‐signaling pathway in SK‐N‐MC neuroblastoma cells. Expression of Tat decreased cell growth and induced apoptosis. Our results revealed dysregulation of various steps involved in the NGF pathway including suppression of MAPK, and inhibition of the promoter activity of Egr‐1, a key pleiotropic mediator of the expression of genes involved in cell growth upon expression of Tat in SK‐N‐MC cells. Similarly, exposure of SK‐N‐MC to conditioned media derived from cells expressing Tat decreased phosphorylation of MAPK and reduced the level of Egr‐1 protein expression in SK‐N‐MC cells. Furthermore, MAPK was able to phosphorylate Purα, a cellular protein that plays an important role in neuronal cell function and differentiation, and this was inhibited by Tat. The ability of Purα to interact with a GA/GC‐rich sequence positioned upstream from the transcription start site of the Egr‐1 promoter provided a rationale to examine Egr‐1 expression. Expression of Tat decreased NGF‐induced Egr‐1 levels in SK‐N‐MC cells and reduced binding of Purα to the Egr‐1 promoter. All of these observations support a model where the interplay between Tat and Purα dysregulates the NGF pathway including the MAPK/Erk network, resulting in reduced expression and activity of Egr‐1 in neuronal cells. J. Cell. Physiol. 208: 506–515, 2006. © 2006 Wiley‐Liss, Inc.

📜 SIMILAR VOLUMES

HIV-1 Tat inhibits NGF-Induced Egr-1 tra
HIV-1 Tat inhibits NGF-Induced Egr-1 transcriptional activity and consequent p35 expression in neural cells
✍ Nune Darbinian; Armine Darbinyan; Marta Czernik; Francesca Peruzzi; Kamel Khalil 📂 Article 📅 2008 🏛 John Wiley and Sons 🌐 English ⚖ 192 KB

## Abstract Infection with HIV‐1 causes degeneration of neurons leading to motor and cognitive dysfunction in AIDS patients. One of the key viral regulatory proteins, Tat, which is released by infected cells, can be taken up by various uninfected cells including neurons and by dysregulating several

Expression of Hoxa-1 and Hoxb-7 is regul
Expression of Hoxa-1 and Hoxb-7 is regulated by extracellular matrix-dependent signals in mammary epithelial cells
✍ Anabella Srebrow; Yael Friedmann; Ali Ravanpay; Charles W. Daniel; Mina J. Bisse 📂 Article 📅 1998 🏛 John Wiley and Sons 🌐 English ⚖ 377 KB 👁 2 views

Homeobox-containing genes encode transcriptional regulators involved in cell fate and pattern formation during embryogenesis. Recently, it has become clear that their expression in continuously developing adult tissues, as well as in tumorigenesis, may be of equal importance. In the mouse mammary gl

Expression of Hoxa-1 and Hoxb-7 is regul
Expression of Hoxa-1 and Hoxb-7 is regulated by extracellular matrix-dependent signals in mammary epithelial cells. J Cell Biochem 69:377–391.
✍ A. Srebrow; Y. Friedmann; A. Ravanpay; C.W. Daniel; M.J. Bissell 📂 Article 📅 1998 🏛 John Wiley and Sons 🌐 English ⚖ 130 KB 👁 2 views

In Figure 3 on pages 384 and Figure 4 on page 385, two labels were misprinted. The top label on the right side of Figure 3B should have been Hoxb-7 instead of Hoxb-1, and the center label of Figure 4B should have been Hoxb-7 instead of Hoxa-7. The corrected figures are reprinted on the following pag