Tags

Type your tag names separated by a space and hit enter

NF-Y is essential for expression of the proapoptotic bim gene in sympathetic neurons.
Cell Death Differ 2011; 18(6):937-47CD

Abstract

Neuronal apoptosis has a major role during development and aberrant apoptosis contributes to the pathology of certain neurological conditions. Studies with nerve growth factor (NGF)-dependent sympathetic neurons have provided important insights into the molecular mechanisms of neuronal apoptosis and the signalling pathways that regulate the cell death programme in neurons. The BH3-only protein Bim is a critical mediator of apoptosis in many cell types and in sympathetic neurons is required for NGF withdrawal-induced death. However, regulation of bim expression is complex and remains incompletely understood. We report that a conserved inverted CCAAT box (ICB) in the rat bim promoter is bound by the heterotrimeric transcription factor NF-Y. Interestingly, NF-Y is required for bim promoter activity and its induction following NGF withdrawal. We demonstrate that NF-Y activity is essential for endogenous Bim expression and contributes to NGF withdrawal-induced death. Furthermore, we find that the transcriptional coactivators CBP and p300 interact with NF-Y and FOXO3a and bind to this region of the bim promoter. The amount of CBP/p300 bound to bim increases after NGF deprivation and inhibition of CBP/p300 activity reduces bim induction. Our results indicate that NF-Y cooperates with FOXO3a to recruit CBP/p300 to the bim promoter to form a stable multi-protein/DNA complex that activates bim transcription after survival factor withdrawal.

Authors+Show Affiliations

Molecular Haematology and Cancer Biology Unit, Institute of Child Health, University College London, London, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21164521

Citation

Hughes, R, et al. "NF-Y Is Essential for Expression of the Proapoptotic Bim Gene in Sympathetic Neurons." Cell Death and Differentiation, vol. 18, no. 6, 2011, pp. 937-47.
Hughes R, Kristiansen M, Lassot I, et al. NF-Y is essential for expression of the proapoptotic bim gene in sympathetic neurons. Cell Death Differ. 2011;18(6):937-47.
Hughes, R., Kristiansen, M., Lassot, I., Desagher, S., Mantovani, R., & Ham, J. (2011). NF-Y is essential for expression of the proapoptotic bim gene in sympathetic neurons. Cell Death and Differentiation, 18(6), pp. 937-47. doi:10.1038/cdd.2010.166.
Hughes R, et al. NF-Y Is Essential for Expression of the Proapoptotic Bim Gene in Sympathetic Neurons. Cell Death Differ. 2011;18(6):937-47. PubMed PMID: 21164521.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NF-Y is essential for expression of the proapoptotic bim gene in sympathetic neurons. AU - Hughes,R, AU - Kristiansen,M, AU - Lassot,I, AU - Desagher,S, AU - Mantovani,R, AU - Ham,J, Y1 - 2010/12/17/ PY - 2010/12/18/entrez PY - 2010/12/18/pubmed PY - 2011/8/23/medline SP - 937 EP - 47 JF - Cell death and differentiation JO - Cell Death Differ. VL - 18 IS - 6 N2 - Neuronal apoptosis has a major role during development and aberrant apoptosis contributes to the pathology of certain neurological conditions. Studies with nerve growth factor (NGF)-dependent sympathetic neurons have provided important insights into the molecular mechanisms of neuronal apoptosis and the signalling pathways that regulate the cell death programme in neurons. The BH3-only protein Bim is a critical mediator of apoptosis in many cell types and in sympathetic neurons is required for NGF withdrawal-induced death. However, regulation of bim expression is complex and remains incompletely understood. We report that a conserved inverted CCAAT box (ICB) in the rat bim promoter is bound by the heterotrimeric transcription factor NF-Y. Interestingly, NF-Y is required for bim promoter activity and its induction following NGF withdrawal. We demonstrate that NF-Y activity is essential for endogenous Bim expression and contributes to NGF withdrawal-induced death. Furthermore, we find that the transcriptional coactivators CBP and p300 interact with NF-Y and FOXO3a and bind to this region of the bim promoter. The amount of CBP/p300 bound to bim increases after NGF deprivation and inhibition of CBP/p300 activity reduces bim induction. Our results indicate that NF-Y cooperates with FOXO3a to recruit CBP/p300 to the bim promoter to form a stable multi-protein/DNA complex that activates bim transcription after survival factor withdrawal. SN - 1476-5403 UR - https://www.unboundmedicine.com/medline/citation/21164521/NF_Y_is_essential_for_expression_of_the_proapoptotic_bim_gene_in_sympathetic_neurons_ L2 - http://dx.doi.org/10.1038/cdd.2010.166 DB - PRIME DP - Unbound Medicine ER -