RGD Reference Report - Pancortin-2 interacts with WAVE1 and Bcl-xL in a mitochondria-associated protein complex that mediates ischemic neuronal death. - Rat Genome Database

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Pancortin-2 interacts with WAVE1 and Bcl-xL in a mitochondria-associated protein complex that mediates ischemic neuronal death.

Authors: Cheng, A  Arumugam, TV  Liu, D  Khatri, RG  Mustafa, K  Kwak, S  Ling, HP  Gonzales, C  Xin, O  Jo, DG  Guo, Z  Mark, RJ  Mattson, MP 
Citation: Cheng A, etal., J Neurosci. 2007 Feb 14;27(7):1519-28.
RGD ID: 11353792
Pubmed: PMID:17301160   (View Abstract at PubMed)
PMCID: PMC6673736   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.5154-06.2007   (Journal Full-text)

The actin-modulating protein Wiskott-Aldrich syndrome protein verprolin homologous-1 (WAVE1) and a novel CNS-specific protein, pancortin, are highly enriched in adult cerebral cortex, but their functions are unknown. Here we show that WAVE1 and pancortin-2 interact in a novel cell death cascade in adult, but not embryonic, cerebral cortical neurons. Focal ischemic stroke induces the formation of a protein complex that includes pancortin-2, WAVE1, and the anti-apoptotic protein Bcl-xL. The three-protein complex is associated with mitochondria resulting in increased association of Bax with mitochondria, cytochrome c release, and neuronal apoptosis. In pancortin null mice generated using a Cre-loxP system, ischemia-induced WAVE1-Bcl-xL interaction is diminished, and cortical neurons in these mice are protected against ischemic injury. Thus, pancortin-2 is a mediator of ischemia-induced apoptosis of neurons in the adult cerebral cortex and functions in a novel mitochondrial/actin-associated protein complex that sequesters Bcl-xL.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Stroke  ISOBcl2l1 (Mus musculus)11353792; 11353792protein:altered localization:cerebral cortex (mouse)RGD 
Stroke  IEP 11353792protein:altered localization:cerebral cortex (mouse)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bcl2l1  (Bcl2-like 1)

Genes (Mus musculus)
Bcl2l1  (BCL2-like 1)

Genes (Homo sapiens)
BCL2L1  (BCL2 like 1)


Additional Information