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Bim is a direct target of a neuronal E2F-dependent apoptotic pathway.
J Neurosci 2005; 25(37):8349-58JN

Abstract

The inappropriate expression/activation of cell-cycle-related molecules is associated with neuron death in many experimental paradigms and human neuropathologic conditions. However, the means whereby this links to the core apoptotic machinery in neurons have been unclear. Here, we show that the pro-apoptotic Bcl-2 homology 3 domain-only molecule Bcl-2 interacting mediator of cell death (Bim) is a target of a cell-cycle-related apoptotic pathway in neuronal cells. Induction of Bim in NGF-deprived cells requires expression and activity of cyclin-dependent kinase 4 (cdk4) and consequent de-repression of E2 promoter binding factor (E2F)-regulated genes including members of the myb transcription factor family. The Bim promoter contains two myb binding sites, mutation of which abolishes induction of a Bim promoter-driven reporter by NGF deprivation or E2F-dependent gene de-repression. NGF deprivation significantly increases endogenous levels of C-myb and its occupancy of the endogenous Bim promoter. These findings support a model in which apoptotic stimuli lead to cdk4 activation, consequent de-repression of E2F-regulated mybs, and induction of pro-apoptotic Bim.

Authors+Show Affiliations

Department of Pathology, Center for Neurobiology and Behavior, Taub Center for Alzheimer's Disease Research, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. scb34@columbia.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

16162916

Citation

Biswas, Subhas C., et al. "Bim Is a Direct Target of a Neuronal E2F-dependent Apoptotic Pathway." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 25, no. 37, 2005, pp. 8349-58.
Biswas SC, Liu DX, Greene LA. Bim is a direct target of a neuronal E2F-dependent apoptotic pathway. J Neurosci. 2005;25(37):8349-58.
Biswas, S. C., Liu, D. X., & Greene, L. A. (2005). Bim is a direct target of a neuronal E2F-dependent apoptotic pathway. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 25(37), pp. 8349-58.
Biswas SC, Liu DX, Greene LA. Bim Is a Direct Target of a Neuronal E2F-dependent Apoptotic Pathway. J Neurosci. 2005 Sep 14;25(37):8349-58. PubMed PMID: 16162916.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bim is a direct target of a neuronal E2F-dependent apoptotic pathway. AU - Biswas,Subhas C, AU - Liu,David X, AU - Greene,Lloyd A, PY - 2005/9/16/pubmed PY - 2006/3/7/medline PY - 2005/9/16/entrez SP - 8349 EP - 58 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 25 IS - 37 N2 - The inappropriate expression/activation of cell-cycle-related molecules is associated with neuron death in many experimental paradigms and human neuropathologic conditions. However, the means whereby this links to the core apoptotic machinery in neurons have been unclear. Here, we show that the pro-apoptotic Bcl-2 homology 3 domain-only molecule Bcl-2 interacting mediator of cell death (Bim) is a target of a cell-cycle-related apoptotic pathway in neuronal cells. Induction of Bim in NGF-deprived cells requires expression and activity of cyclin-dependent kinase 4 (cdk4) and consequent de-repression of E2 promoter binding factor (E2F)-regulated genes including members of the myb transcription factor family. The Bim promoter contains two myb binding sites, mutation of which abolishes induction of a Bim promoter-driven reporter by NGF deprivation or E2F-dependent gene de-repression. NGF deprivation significantly increases endogenous levels of C-myb and its occupancy of the endogenous Bim promoter. These findings support a model in which apoptotic stimuli lead to cdk4 activation, consequent de-repression of E2F-regulated mybs, and induction of pro-apoptotic Bim. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/16162916/Bim_is_a_direct_target_of_a_neuronal_E2F_dependent_apoptotic_pathway_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=16162916 DB - PRIME DP - Unbound Medicine ER -