RGD Reference Report - BAG3 protein is overexpressed in human glioblastoma and is a potential target for therapy. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

BAG3 protein is overexpressed in human glioblastoma and is a potential target for therapy.

Authors: Festa, M  Del Valle, L  Khalili, K  Franco, R  Scognamiglio, G  Graziano, V  De Laurenzi, V  Turco, MC  Rosati, A 
Citation: Festa M, etal., Am J Pathol. 2011 Jun;178(6):2504-12. Epub 2011 May 10.
RGD ID: 5687132
Pubmed: PMID:21561597   (View Abstract at PubMed)
PMCID: PMC3124067   (View Article at PubMed Central)
DOI: DOI:10.1016/j.ajpath.2011.02.002   (Journal Full-text)

Glioblastoma multiforme, which represents 80% of malignant gliomas, is characterized by aggressiveness and high recurrence rates. Despite therapeutic advances, patients with glioblastoma multiforme show a poor survival, and identification of novel markers and molecular targets for therapy is needed. A role for BAG3, a member of the BAG family of HSC/HSP70 co-chaperones, in promoting tumor cell growth in vivo has recently been described. We analyzed BAG3 levels by IHC in specimens from patients affected by brain tumors and we found that BAG3, although negative in normal brain tissues, was highly expressed in astrocytic tumors and increasingly expressed in more aggressive types of cancer; it was particularly high in glioblastomas. Down-regulating BAG3 both in vitro and in vivo in a rat glioblastoma model resulted in increased sensitivity to apoptosis, suggesting that BAG3 is a potential target for novel therapies. Finally, we determined that the underlying molecular mechanism requires the formation of a complex of BAG3, HSP70, and BAX that prevents BAX translocation to mitochondria, thus protecting tumor cells from apoptosis. Our data identify BAG3 as a potential marker of glial brain tumor sensitivity to therapy and thus also an attractive candidate for new molecular therapies.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
glioblastoma treatmentISOBag3 (Rattus norvegicus)5687132; 5687132 RGD 
glioblastoma treatmentIMP 5687132 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of apoptotic process  IMP 5687132 RGD 
negative regulation of protein targeting to mitochondrion  IMP 5687132 RGD 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Bag3  (BAG cochaperone 3)
Bax  (BCL2 associated X, apoptosis regulator)
Hspa4  (heat shock protein family A (Hsp70) member 4)

Genes (Mus musculus)
Bag3  (BCL2-associated athanogene 3)

Genes (Homo sapiens)
BAG3  (BAG cochaperone 3)


Additional Information