Adenovirus E1B 19 kDa and Bcl-2 proteins interact with a common set of cellular proteins

Boyd, Janice M.; Malstrom, Scott; Subramanian, T.; Venkatesh, Leelavathi; Schaeper, Ute; Elangovan, B.; D'Sa-Eipper, Cleta; Chinnadurai, G.

doi:10.1016/0092-8674(94)90202-x

Cited by 452 publications

(353 citation statements)

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“…BNIP3 was originally identified using a yeast two-hybrid screen for proteins that bind to the adenoviral E1B 19-kDa protein (Boyd et al, 1994). The protein contains a BH3 domain that induces apoptosis (Yasuda et al, 1998) and a C-terminal transmembrane domain that is required for both its mitochondrial localisation and its proapoptotic activity (Chen et al, 1997(Chen et al, , 1999Yasuda et al, 1998); it has been suggested that BNIP3 mediates a necrosis-like cell death by causing mitochondrial dysfunction (Harris, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…First identified via its interaction with adenovirus E1B 19-kDa and Bcl-2, BNIP3 is one of the Bcl-2 homology 3 (BH3)-only subfamily of Bcl-2 proteins, which display proapoptotic activity (Boyd et al, 1994). Forced expression of BNIP3 induces cell death characterised by localisation of the protein at the mitochondria, opening of the permeability transition pore, loss of membrane potential and production of reactive oxygen species (Regula et al, 2002;Vande Velde et al, 2000).…”

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Aberrant DNA methylation associated with silencing BNIP3 gene expression in haematopoietic tumours

et al. 2005

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Hypoxia is a key factor contributing to the progression of human neoplasias and to the development of resistance to chemotherapy. BNIP3 is a proapoptotic member of the Bcl-2 protein family involved in hypoxia-induced cell death. We evaluated the expression and methylation status of BNIP3 gene to better understand the role of epigenetic alteration of its expression in haematopoietic tumours. Methylation of the region around the BNIP3 transcription start site was detected in four acute lymphocytic leukaemia, one multiple myeloma and one Burkitt lymphoma cell lines, and was closely associated with silencing the gene. That expression of BNIP3 was restored by treatment with 5-aza2 0 -deoxycytidine (5-aza-dC), a methyltransferase inhibitor, which confirmed the gene to be epigenetically inactivated by methylation. Notably, re-expression of BNIP3 using 5-aza2-dC also restored hypoxia-mediated cell death in methylated cell lines. Acetylation of histone H3 in the 5 0 region of the gene, which was assessed using chromatin immunoprecipitation assays, correlated directly with gene expression and inversely with DNA methylation. Among primary tumours, methylation of BNIP3 was detected in five of 34 (15%) acute lymphocytic leukaemias, six of 35 (17%) acute myelogenous leukaemias and three of 14 (21%) multiple myelomas. These results suggest that aberrant DNA methylation of the 5 0 CpG island and histone deacetylation play key roles in silencing BNIP3 expression in haematopoietic tumours.

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Section: Discussionmentioning

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Aberrant DNA methylation associated with silencing BNIP3 gene expression in haematopoietic tumours

et al. 2005

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“…We have identi®ed and cloned four cellular proteins that interact with viral (E1B-19K and EBV-BHRF1) and cellular (BCL-2 and BCL-X L ) BCL-2 family anti-apoptosis proteins (Boyd et al, 1994(Boyd et al, , 1995. These proteins include BIK, the founding member of the`BH3-alone' pro-apoptotic proteins (Boyd et al, 1995;Chittenden et al, 1995;Han et al, 1996), BNIP1, BNIP2 and BNIP3 (Boyd et al, 1994). Among the latter three proteins, BNIP3 has been shown to be a member of the`BH3-alone' proteins (Yasuda et al, 1998a).…”

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“…BNIP3 (Yasuda et al, 1998a;Chen et al, 1997) and its human homolog BNIP3a (Yasuda et al, 1999, Chen et al, 1999Matsushima et al, 1998) as well as the C. elegans homolog, ceBNIP3 (Yasuda et al, 1998b), promote apoptosis. BNIP2 appears to be related to the signaling molecule RhoGAP (Boyd et al, 1994) and it has opposing e ects on apoptosis, depending on the stimuli (X Gong and G Chinnadurai, in preparation). BNIP1 resembles other BCL-2 family proteins since it contains a characteristic C-terminal trans-membrane domain that targets it and certain heterologous proteins to mitochondria and nuclear envelope/ER regions (Boyd et al, 1994;Yasuda et al, 1998a).…”

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confidence: 99%

“…BNIP2 appears to be related to the signaling molecule RhoGAP (Boyd et al, 1994) and it has opposing e ects on apoptosis, depending on the stimuli (X Gong and G Chinnadurai, in preparation). BNIP1 resembles other BCL-2 family proteins since it contains a characteristic C-terminal trans-membrane domain that targets it and certain heterologous proteins to mitochondria and nuclear envelope/ER regions (Boyd et al, 1994;Yasuda et al, 1998a). In this communication, we report that BNIP1 contains a BH3 domain and promotes apoptosis.…”

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Functional identification of the apoptosis effector BH3 domain in cellular protein BNIP1

Yasuda

Chinnadurai

2000

Oncogene

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BCL-2 family proteins: Regulators of cell death involved in the pathogenesis of cancer and resistance to therapy

et al. 1996

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The BCL-2 gene was first discovered because of its involvement in the t(14;18) chromosomal translocations commonly found in lymphomas, which result in deregulation of BCL-2 gene expression and cause inappropriately high levels of Bcl-2 protein production. Expression of the BCL-2 gene can also become altered in human cancers through other mechanisms, including loss of the p53 tumor suppressor which normally functions as a repressor of BCL-2 gene expression in some tissues. Bcl-2 is a blocker of programmed cell death and apoptosis that contributes to neoplastic cell expansion by preventing cell turnover caused by physiological cell death mechanisms, as opposed to accelerating rates of cell division. Overproduction of the Bcl-2 protein also prevents cell death induced by nearly all cytotoxic anticancer drugs and radiation, thus contributing to treatment failures in patients with some types of cancer. Several homologs of Bcl-2 have recently been discovered, some of which function as inhibitors of cell death and others as promoters of apoptosis that oppose the actions of the Bcl-2 protein. Many of these Bcl-2 family proteins can interact through formation of homo- and heterotypic dimers. In addition, several nonhomologous proteins have been identified that bind to Bcl-2 and that can modulate apoptosis. These protein-protein interactions may eventual serve as targets for pharmacologically manipulating the physiological cell death pathway for treatment of cancer and several other diseases.

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Adenovirus E1B 19 kDa and Bcl-2 proteins interact with a common set of cellular proteins

Cited by 452 publications

References 59 publications

Aberrant DNA methylation associated with silencing BNIP3 gene expression in haematopoietic tumours

Aberrant DNA methylation associated with silencing BNIP3 gene expression in haematopoietic tumours

Functional identification of the apoptosis effector BH3 domain in cellular protein BNIP1

BCL-2 family proteins: Regulators of cell death involved in the pathogenesis of cancer and resistance to therapy

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