GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:21252910

From GONUTS
Jump to: navigation, search
Citation

Rodríguez-Aznar, E and Nieto, MA (2011) Repression of Puma by scratch2 is required for neuronal survival during embryonic development. Cell Death Differ. 18:1196-207

Abstract

Although Snail factors promote cell survival in development and cancer, the tumor-suppressor p53 promotes apoptosis in response to stress. p53 and Snail2 act antagonistically to regulate p53 upregulated modulator of apoptosis (Puma) and cell death in hematopoietic progenitors following DNA damage. Here, we show that this relationship is conserved in the developing nervous system in which Snail genes are excluded from vertebrate neurons and they are substituted by Scratch, a related but independent neural-specific factor. The transcription of scratch2 is induced directly by p53 after DNA damage to repress puma, thereby antagonizing p53-mediated apoptosis. In addition, we show that scratch2 is required for newly differentiated neurons to survive by maintaining Puma levels low during normal embryonic development in the absence of damage. scratch2 knockdown in zebrafish embryos leads to neuronal death through the activation of the intrinsic and extrinsic apoptotic pathways. To compensate for neuronal loss, the proliferation of neuronal precursors increases in scratch2-deficient embryos, reminiscent of the activation of progenitor/stem cell proliferation after damage-induced apoptosis. Our data indicate that the regulatory loop linking p53/Puma with Scratch is active in the vertebrate nervous system, not only controlling cell death in response to damage but also during normal embryonic development.

Links

PubMed PMC3131948 Online version:10.1038/cdd.2010.190

Keywords

Animals; Apoptosis Regulatory Proteins/metabolism; DNA Damage; Embryonic Development; Gene Knockdown Techniques; Nervous System/embryology; Neurons/cytology; Neurons/metabolism; Proto-Oncogene Proteins/metabolism; Transcription Factors/antagonists & inhibitors; Transcription Factors/genetics; Transcription Factors/metabolism; Tumor Suppressor Protein p53/antagonists & inhibitors; Tumor Suppressor Protein p53/metabolism; Zebrafish/embryology; Zebrafish/metabolism; Zebrafish Proteins/antagonists & inhibitors; Zebrafish Proteins/genetics; Zebrafish Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DANRE:A4IGB7

involved_in

GO:0043516: regulation of DNA damage response, signal transduction by p53 class mediator

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-070126-7,ZFIN:ZDB-MRPHLNO-110808-4

P

Seeded From UniProt

complete

DANRE:A4IGB7

involved_in

GO:0043523: regulation of neuron apoptotic process

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-110808-4

P

Seeded From UniProt

complete

DANRE:P53

involved_in

GO:0042771: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:Q6YI50

involved_in

GO:0043516: regulation of DNA damage response, signal transduction by p53 class mediator

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-070126-7,ZFIN:ZDB-MRPHLNO-110808-4

P

Seeded From UniProt

complete

DANRE:Q6YI50

involved_in

GO:0043523: regulation of neuron apoptotic process

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-110808-4

P

Seeded From UniProt

complete

DANRE:Q6YI50

enables

GO:0000977: RNA polymerase II transcription regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_at:(SO:0001158)

Seeded From UniProt

complete

DANRE:Q6YI50

enables

GO:0001227: DNA-binding transcription repressor activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_at:(SO:0001158)

Seeded From UniProt

complete

DANRE:Q6YI50

located_in

GO:0000785: chromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DANRE:Q6YI50

enables

GO:0070888: E-box binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_at:(SO:0001158)

Seeded From UniProt

complete

DANRE:Q6YI50

involved_in

GO:1902166: negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator

ECO:0000305: curator inference used in manual assertion

GO:0043516

P

Seeded From UniProt

complete

DANRE:Q6YI50

involved_in

GO:1902042: negative regulation of extrinsic apoptotic signaling pathway via death domain receptors

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:Q6YI50

involved_in

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.