QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (22) Citing Articles via Google Scholar Google Scholar Articles by Levkovitz, Y. Articles by Baraban, J. M. Search for Related Content PubMed PubMed Citation Articles by Levkovitz, Y. Articles by Baraban, J. M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CYTARABINE POTASSIUM

 Previous Article  |  Next Article 

The Journal of Neuroscience, August 15, 2001, 21(16):5893-5901

A Dominant Negative Inhibitor of the Egr Family of Transcription Regulatory Factors Suppresses Cerebellar Granule Cell Apoptosis by Blocking c-Jun Activation

Yechiel Levkovitz and Jay M. Baraban

Departments of Neuroscience, Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

To investigate the role of the Egr family of transcription regulatory factors in neuronal apoptosis, we examined the effect of a dominant negative Egr inhibitor construct in a well characterized in vitro paradigm, cerebellar granule cell death induced by withdrawal of depolarizing concentrations of extracellular potassium. We found that this apoptotic stimulus increases the activity of a reporter gene driven by the Egr response element and that a dominant negative inhibitor of Egr-mediated transcription blocks granule cell apoptosis. In contrast, apoptosis of immature granule cells induced by cytosine arabinoside is not inhibited by the Egr inhibitor construct. Because activation of c-Jun is an essential step in granule cell death induced by potassium deprivation, but not cytosine arabinoside, we asked whether the Egr inhibitor acts by influencing c-Jun activation or its ability to induce apoptosis. We found that the Egr inhibitor does not block the ability of a constitutively active c-Jun construct to induce apoptosis in these cells but does suppress activation of c-Jun-mediated transcription induced by lowering extracellular potassium concentration. Furthermore, the Egr inhibitor blocks the ability of MEKK1 [mitogen-activated protein kinase (MAPK) kinase kinase 1], an upstream kinase capable of stimulating the JNK (c-Jun N-terminal protein kinase)-c-Jun pathway, to induce apoptosis and activate c-Jun. Together, these studies indicate that the Egr family of transcription factors plays a critical role in neuronal apoptosis and identify c-Jun activation as an important downstream target of the Egr family in this process.

Key words: Egr1; zif268; c-Jun; MEKK1; JNK; cytosine arabinoside

---

Copyright © 2001 Society for Neuroscience  0270-6474/01/21165893-09$05.00/0

This article has been cited by other articles:

				Z. Yuan, S. Gong, J. Luo, Z. Zheng, B. Song, S. Ma, J. Guo, C. Hu, G. Thiel, C. Vinson, et al. Opposing Roles for ATF2 and c-Fos in c-Jun-Mediated Neuronal Apoptosis Mol. Cell. Biol., May 1, 2009; 29(9): 2431 - 2442. [Abstract] [Full Text] [PDF]

				C W Li, W Cheung, Z B Lin, T Y Li, J T Lim, and D Y Wang Oral steroids enhance epithelial repair in nasal polyposis via upregulation of the AP-1 gene network Thorax, April 1, 2009; 64(4): 306 - 312. [Abstract] [Full Text] [PDF]

				J. H. Carter and W. G. Tourtellotte Early Growth Response Transcriptional Regulators Are Dispensable for Macrophage Differentiation J. Immunol., March 1, 2007; 178(5): 3038 - 3047. [Abstract] [Full Text] [PDF]

				M.-H. Liang and D.-M. Chuang Differential Roles of Glycogen Synthase Kinase-3 Isoforms in the Regulation of Transcriptional Activation J. Biol. Chem., October 13, 2006; 281(41): 30479 - 30484. [Abstract] [Full Text] [PDF]

				A. M. Monjazeb, K. P. High, A. Connoy, L. S. Hart, C. Koumenis, and F. H. Chilton Arachidonic acid-induced gene expression in colon cancer cells Carcinogenesis, October 1, 2006; 27(10): 1950 - 1960. [Abstract] [Full Text] [PDF]

				K. Eto, V. Kaur, and M. K. Thomas Regulation of Insulin Gene Transcription by the Immediate-Early Growth Response Gene Egr-1 Endocrinology, June 1, 2006; 147(6): 2923 - 2935. [Abstract] [Full Text] [PDF]

				B. Drisaldi, J. Coomaraswamy, P. Mastrangelo, B. Strome, J. Yang, J. C. Watts, M. A. Chishti, M. Marvi, O. Windl, R. Ahrens, et al. Genetic Mapping of Activity Determinants within Cellular Prion Proteins: N-TERMINAL MODULES IN PrPC OFFSET PRO-APOPTOTIC ACTIVITY OF THE DOPPEL HELIX B/B' REGION J. Biol. Chem., December 31, 2004; 279(53): 55443 - 55454. [Abstract] [Full Text] [PDF]

				R. K. Giri, S. K. Selvaraj, and V. K. Kalra Amyloid Peptide-Induced Cytokine and Chemokine Expression in THP-1 Monocytes Is Blocked by Small Inhibitory RNA Duplexes for Early Growth Response-1 Messenger RNA J. Immunol., May 15, 2003; 170(10): 5281 - 5294. [Abstract] [Full Text] [PDF]

				Y. Konishi and A. Bonni The E2F-Cdc2 Cell-Cycle Pathway Specifically Mediates Activity Deprivation-Induced Apoptosis of Postmitotic Neurons J. Neurosci., March 1, 2003; 23(5): 1649 - 1658. [Abstract] [Full Text] [PDF]

				Y. Levkovitz and J. M. Baraban A Dominant Negative Egr Inhibitor Blocks Nerve Growth Factor-Induced Neurite Outgrowth by Suppressing c-Jun Activation: Role of an Egr/c-Jun Complex J. Neurosci., May 15, 2002; 22(10): 3845 - 3854. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help