GRS, a novel member of the Bcl-2 gene family, is highly expressed in multiple cancer cell lines and in normal leukocytes

Kenny, Joseph J.; Knobloch, Thomas J.; Augustus, Meena; Carter, Kenneth C.; Rosen, Craig A.; Lang, Jas C.

doi:10.1038/sj.onc.1200898

Cited by 30 publications

(26 citation statements)

References 15 publications

(17 reference statements)

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“…This activity of BFL-1 may have an important implication in oncogenesis. Since BFL-1 and the related protein GRS, are overexpressed in several human malignancies of epithelial (Choi et al, 1995) and hematopoietic origin (Kenny et al, 1997), the proliferation facilitating activity in addition to its antiapoptosis activity may contribute to the ontogeny of some of these malignancies. The proliferation facilitating activity of wt BFL-1 that we have discovered here, contributes to the enhanced in vitro oncogene cooperating activity (compared to other BCL-2 family members) that we have reported earlier .…”

Section: Discussionmentioning

confidence: 99%

“…The BFL-1 protein shares about 72% amino acid identity with mouse A1 protein and therefore both proteins may be considered homologs. Another BCL-2 family member, designated GRS, closely related to BFL-1 (diering in two amino acid positions) has also been identi®ed (Kenny et al, 1997). BFL-1 and GRS are abundantly expressed in normal bone marrow cells and leukocytes and are activated in certain tumors such as gastrointestinal tumors (Choi et al, 1995) and hematopoietic malignancies (Kenny et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

“…Another BCL-2 family member, designated GRS, closely related to BFL-1 (diering in two amino acid positions) has also been identi®ed (Kenny et al, 1997). BFL-1 and GRS are abundantly expressed in normal bone marrow cells and leukocytes and are activated in certain tumors such as gastrointestinal tumors (Choi et al, 1995) and hematopoietic malignancies (Kenny et al, 1997). We have previously reported that B¯-1 eciently suppresses apoptosis and exhibits a potent oncogene cooperating activity (D'SaEipper et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

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Functional dissection of Bfl-1, a Bcl-2 homolog: anti-apoptosis, oncogene-cooperation and cell proliferation activities

D'Sa-Eipper

Chinnadurai

1998

Oncogene

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Functional dissection of Bfl-1, a Bcl-2 homolog: anti-apoptosis, oncogene-cooperation and cell proliferation activities

D'Sa-Eipper

Chinnadurai

1998

Oncogene

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“…The first cDNA clones of A1 were identified from mouse bone marrow as a granulocyte macrophage-colony stimulating factor-inducible Bcl-2 related gene 376 and were later cloned in fetal liver 369 , activated endothelial cells after cytokine treatment 370 , and myeloid leukaemia 377 . There is some confliction in the literature as to the expression pattern of Bfl-1, possibly through a difference in murine and human expression patterns.…”

Section: The Role Of Bfl-1 In Healthy Tissuesmentioning

confidence: 99%

Role of the pro-survival molecule Bfl-1 in melanoma

Hind

Carter

Harris

et al. 2015

The International Journal of Biochemistry & Cell Biology

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Melanoma, the cancer derived from the melanocytes of the skin, is becoming an ever more common cancer in the ageing population of the developed world and displays an intrinsic resistance to current therapies. This chemo resistance makes metastatic melanoma an extremely difficult cancer to treat leading to a 5 year survival rate of just 20%. As such, it is important to unearth new potential drug targets to increase the prospects for melanoma patients.Bfl-1 is a pro-survival protein of the Bcl-2 family of apoptosis regulating proteins. It has been found to be over-expressed in a small subset of chemo resistant tumours, including melanoma. Accordingly, I characterised the molecule in melanoma cells and determined its role in protecting these cells from chemotherapy-induced apoptosis. I elucidated the expression profile and half-lives of the protein and mRNA across a panel of melanoma cell-lines and healthy melanocytes. I also confirmed, using pathway specific inhibitors, that Bfl-1 was transcriptionally regulated by the NFB pathway and concluded through pulsechase experiments that Bfl-1 protein was degraded, at least in part, by the proteasome. Subcellular fractionation and indirect immunofluorescence techniques elucidated that Bfl-1 was located mostly at the mitochondria in both resting and apoptotic cells, with a diffuse level present throughout the cytoplasm. As well as characterising the protein in both melanoma cells and healthy primary melanocytes, I determined its role in the resistance of these cells to apoptosis. Over-expressed Bfl-1 was found to protect melanoma cells from apoptosis caused by a range of chemotherapeutic agents in A375 melanoma cells, which naturally expressed very low levels of Bfl-1. Further, knock down of Bfl-1 using siRNA technology in melanoma cells revealed the dependence of these cells on Bfl-1 for their resistance to certain chemotherapeutic agents currently used in melanoma treatment, including the MEK inhibitor PD901. All together, this research contributes to our understanding of Bfl-1 and highlights it as a potentially important therapeutic target in metastatic melanoma.

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“…32,33 Once constructed, a panel of B-LCLs, including those transduced with HLA cDNAs, could be commonly applied to immunophenotyping with different CTL clones, especially when Finally, the discovery of ACC-1 C as a novel minor H antigen indicates that all the mismatched transplants at this locus could be eligible for allo-immune therapies, since we have previously demonstrated that the counter allele also encodes a minor H antigen, ACC-1 Y , which is preferentially expressed and presented on blood components including leukemic cells and may serve as a target of allo-immunity. 7,34 Indeed, CTLs specific for ACC-2, an HLA-B44-restricted minor H antigen restricted by the third exonic SNP on BCL2A1, 7 was independently isolated from the peripheral blood of a patient with recurrent leukemia re-entering complete remission after donor lymphocyte infusion. 32 The number of eligible allo-HSCT recipients has now been effectively doubled, accounting for 50% of transplants with HLA-A24 or 20% of all transplantations performed in the Asian population.…”

Section: Discussionmentioning

confidence: 99%

Identification of human minor histocompatibility antigens based on genetic association with highly parallel genotyping of pooled DNA

Kawase

Nannya

Torikai³

et al. 2008

Blood

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Minor histocompatibility (H) antigens are the molecular targets of allo-immunity responsible both for the development of antitumor effects and for graft-versushost disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, despite their potential clinical use, our knowledge of human minor H antigens is largely limited by the lack of efficient methods of their characterization. Here we report a robust and efficient method of minor H gene discovery that combines whole genome association scans (WGASs) with cytotoxic Tlymphocyte (CTL) assays, in which the genetic loci of minor H genes recognized by the CTL clones are precisely identified using pooled-DNA analysis of immortalized lymphoblastoid cell lines with/without susceptibility to those CTLs. Using this method, we have successfully mapped 2 loci: one previously characterized (HMSD encoding ACC-6), and one novel. The novel minor H antigen encoded by BCL2A1 was identified within a 26 kb linkage disequilibrium block on chromosome 15q25, which had been directly mapped by WGAS. The pool size required to identify these regions was no more than 100 individuals. Thus, once CTL clones are generated, this method should substantially facilitate discovery of minor H antigens applicable to targeted allo-immune therapies and also contribute to our understanding of human allo-immunity. (Blood. 2008;111: 3286-3294)

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GRS, a novel member of the Bcl-2 gene family, is highly expressed in multiple cancer cell lines and in normal leukocytes

Cited by 30 publications

References 15 publications

Functional dissection of Bfl-1, a Bcl-2 homolog: anti-apoptosis, oncogene-cooperation and cell proliferation activities

Functional dissection of Bfl-1, a Bcl-2 homolog: anti-apoptosis, oncogene-cooperation and cell proliferation activities

Role of the pro-survival molecule Bfl-1 in melanoma

Identification of human minor histocompatibility antigens based on genetic association with highly parallel genotyping of pooled DNA

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