Small G proteins are expressed ubiquitously in lymphoid cells and do not correspond to Bcl-2

Monica, K; Chen-Levy, Zehava; Cleary, Michael L.

doi:10.1038/346189a0

Cited by 19 publications

(6 citation statements)

References 24 publications

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“…It has been suggested (Haldar et a/.. 1989) that be/-2 is a G-protein, but this work has not been confirmed (Monica et al, 1990). The intracellular localization of the protein to mitochondria, as reported recently , led to speculation that bcl-2 might modulate the metabolic functions of the inner mitochondrial membrane.…”

Section: Discussionmentioning

confidence: 89%

Prevention of programmed cell death in burkitt lymphoma cell lines by bcl‐2‐dependent and ‐independent mechanisms

Milner

Johnson

Gregory

1992

Intl Journal of Cancer

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Burkitt lymphoma (BL) cell lines which retain the phenotypic characteristics of the freshly-isolated tumour cells (group I cells) readily enter programmed cell death (apoptosis) in response to a variety of triggers. By contrast, isogenic BL cells which are phenotypically altered as a result of activation of their resident EBV genome (group-III cells) are highly protected from apoptosis. Phenotypic changes in group-III cells include the up-regulation of the oncogene, bcl-2. Expression of the 26-kDa bcl-2 protein in group-I BL cells following gene transfer was found to afford protection from apoptosis: the degree of protection was proportional to the amount of bcl-2 protein expressed. When group-I bcl-2 transfectants were compared with their group-III counterparts it was found that, whilst bcl-2 made a significant contribution in protecting from entry into apoptosis, hyper-expression of bcl-2 protein in group-I cells (well beyond that of group-III cells) was necessary to attain the high levels of protection observed in group-III cells. These results suggested that additional, bcl-2-independent, survival mechanisms could operate in BL cells. In support of this notion it was also found that: (1) prolonged culture of group-I lines in vitro resulted in enhanced survival in the absence of bcl-2 up-regulation, and (2) exposure of group-I cells to interferon-alpha triggered a bcl-2-independent protective response. The molecular mechanisms of both the bcl-2-dependent and -independent survival pathways remain to be determined.

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Section: Discussionmentioning

confidence: 89%

Prevention of programmed cell death in burkitt lymphoma cell lines by bcl‐2‐dependent and ‐independent mechanisms

Milner

Johnson

Gregory

1992

Intl Journal of Cancer

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“…Bcl-2a is not itself a GTP-binding protein (Monica et al, 1990), but coprecipitates with R-Ras, a member of the Ras family of small G-proteins, when either is immunoprecipitated (Fernandez-Sarabia and Bischoff, 1993). Bcl-2a also coprecipitates with Raf-1 (Wang et al, 1994a), a serinekhreonine kinase that itself binds to and is activated by H-Ras in a GTP-dependent manner and in turn activates the microtubule-associated protein kinase cascade.…”

Section: Possible Mechanisms Of Action Of Bcl-2 the Mechanism(s)mentioning

confidence: 99%

Apoptosis: Molecular Regulation of Cell Death

Hale

Smith

Sutherland

et al. 1996

European Journal of Biochemistry

601

221

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The field of apoptosis is unusual in several respects. Firstly, its general importance has been widely recognised only in the past few years and its surprising significance is still being evaluated in a number of areas of biology. Secondly, although apoptosis is now accepted as a critical element in the repertoire of potential cellular responses, the picture of the intra‐cellular processes involved is probably still incomplete, not just in its details, but also in the basic outline of the process as a whole. It is therefore a very interesting and active area at present and is likely to progress rapidly in the next two or three years. This review emphasises recent work on the molecular mechanisms of apoptosis and, in particular, on the intracellular interactions which control this process. This latter area is of crucial importance since dysfunction of the normal control machinery is likely to have serious pathological consequences, probably including oncogenesis, autoimmunity and degenerative disease. The genetic analysis of programmed cell death during the development of the nematode Caenorhabditis elegans has proved very useful in identifying important events in the cell death programme. Recently defined genetic connections between C. elegans cell death and mammalian apoptosis have emphasized the value of this system as a model for cell death in mammalian cells, which, inevitably, is more complex. The signals inducing apoptosis are very varied‐and the same signals can induce differentiation and proliferation in other situations. However, some pathways appear to be of particular significance in the control of cell death; recent analysis of the apoptosis induced through the cell‐surface Fas receptor has been especially important for immunology. Two gene families are dealt with in particular detail because of their likely importance in apoptosis control. These are, first, the genes encoding the interleukin‐1β‐converting enzyme family of cysteine proteases and, second, those related to the proto‐oncogene bcl‐2. Both of these families are homologous to cell death genes in C. elegans. In mammalian cells the number of members of both families which have been identified is growing rapidly and considerable effort is being directed towards establishing the roles played by each member and the ways in which they interact to regulate apoptosis. Other genes with established roles in the regulation of proliferation and differentiation are also important in controlling apoptosis. Several of these are known proto‐oncogenes, e.g. c‐myc, or tumour suppressors, e.g. p.53, an observation which is consistent with the importance of defective apoptosis in the development of cancer. Viral manipulation of the apoptosis of host cells frequently involves interactions with these cellular proteins. Finally, the biochemistry of the closely controlled cellular self‐destruction which ensues when the apoptosis programme has been engaged is also very important. The biochemical changes involved in inducing phagocytosis of the apoptotic cell, for e...

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“…Cell extracts were prepared by using RIPA buffer (see above). Protein fractions containing 2 x 105 cell equivalents were subjected to 10% SDS-PAGE and electrotransferred to nitrocellulose by using transfer buffer as described elsewhere (44). Filters were then subjected to Western blot (immunoblot) analysis with anti-Pbxla antibodies as previously described (6).…”

Section: Methodsmentioning

confidence: 99%

PBX2 and PBX3, new homeobox genes with extensive homology to the human proto-oncogene PBX1.

et al. 1991

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Two new homeobox genes, PBX2 and PBX3, were isolated on the basis of their extensive homology to PBX], a novel human homeobox gene involved in t(l;19) translocation in acute pre-B-cell leukemias. The A sequence of 180 bp termed the homeobox was initially discovered as a conserved segment of the Antennapedia, Ultrabithorax, and fushi tarazu transcription units (40,41,53). Subsequently, homeoboxes have been observed in the genomes of many species by cross-hybridization and have also been found fortuitously in genes isolated by other means. Homeoboxes code for a conserved protein motif, termed the homeodomain, and the degree of similarity between different homeodomains has been used to group them into related classes (52). While most of the Drosophila homeodomain proteins have been implicated in developmental processes, the functions of the majority of non-Drosophila homeodomain proteins remain unknown. However, because of the presence of homeodomains in known transcription factors and the structural similarity between the homeodomain and DNA-binding motifs in bacterial proteins, the current view is that most if not all of these proteins function as sequence-specific DNA-binding proteins that likely play an important role in transcriptional regulation (for reviews, see references 17 and 52).Recently, a novel human homeobox gene, PBXJ, was identified because of its involvement in t(1;19) chromosomal translocation in acute pre-B-cell leukemias (29,47). This translocation results in the formation of a fusion transcript that codes for E2A-Pbxl chimeric proteins, in which the C-terminal region of E2A, which contains its basic and helix-loop-helix (bHLH) DNA-binding and dimerization motifs, is replaced by sequences from Pbxl that contain a highly divergent homeodomain. The role of E2A-Pbx chimeric transcription factors in the pathogenesis of acute pre-B-cell leukemias remains unknown.Considering the high level of divergence between Pbxl and previously reported homeodomains, we hypothesized that there may be additional, as-yet-uncharacterized homeobox genes which encode homeodomains similar to that * Corresponding author.of Pbxl. We describe here the characterization of two such genes, designated PBX2 and PBX3, which were isolated as a result of their cross-hybridization with the PBX] homeobox. A striking feature of the Pbxl, Pbx2, and Pbx3 proteins is their extensive sequence identity both within and outside of their homeodomains. The similarities in their structures and patterns of expression suggest a generalized, overlapping function for Pbx homeodomain proteins in most cell types. MATERIALS AND METHODSIsolation and sequencing of PBX2 and PBX3 cDNA clones. PBX2 and PBX3 cDNA clones were identified by screening a HeLa cDNA library under nonstringent conditions with a PBXJ homeobox probe (nucleotides 1951 to 2210) (47). Library filters containing phage DNA were prehybridized overnight at 37°C in 43% formamide, 5x SSC (lx SSC is 0.15 M NaCl with 0.015 M sodium citrate), 5x Denhardt's solution, 1 mM sodium pyrophosphate...

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Small G proteins are expressed ubiquitously in lymphoid cells and do not correspond to Bcl-2

Cited by 19 publications

References 24 publications

Prevention of programmed cell death in burkitt lymphoma cell lines by bcl‐2‐dependent and ‐independent mechanisms

Prevention of programmed cell death in burkitt lymphoma cell lines by bcl‐2‐dependent and ‐independent mechanisms

Apoptosis: Molecular Regulation of Cell Death

PBX2 and PBX3, new homeobox genes with extensive homology to the human proto-oncogene PBX1.

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