Loss of cell cycle controls in apoptotic lymphoblasts of the bursa of Fabricius.

Neiman, Paul E.; Blish, Catherine A.; Heydt, Colin; Loring, Gilbert; Thomas, Spencer A.

doi:10.1091/mbc.5.7.763

Cited by 13 publications

(8 citation statements)

References 35 publications

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“…Consequently, the inhibition of apoptosis observed in the mammary gland following overexpression of des(1-3)hIGF-I was not unexpected. The decrease observed in DNA synthesis in the mammary glands of WAP-DES mice probably re¯ects the fact that entry into S phase is often a prerequisite for programmed cell death (Neiman et al, 1994). This is also consistent with the observed decrease in apoptosis.…”

Section: Tumorigenesis In the Wap-des Micesupporting

confidence: 85%

Cooperative interaction between mutant p53 and des(1-3)IGF-I accelerates mammary tumorigenesis

et al. 2000

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Mammary tumorigenesis was analysed in transgenic mice which overexpress des(1-3)hIGF-I (WAP-DES) and/or a mutant form of p53 (p53 172R-H ). Nonlactating, multiparous WAP-DES mice exhibited hyperplastic lesions termed mammary interepithelial neoplasia (MIN) which constitutively expressed WAP-DES. By 23 months of age, 53% of the WAP-DES mice developed mammary adenocarcinomas. A 75% reduction in both apoptosis and proliferation was observed in the normal mammary glands of WAP-DES mice. Mammary tumor incidence in WAP-DES/p53 bitransgenic mice was similar to that of WAP-DES and 2 ± 3-fold greater than that of nontransgenic and p53 172R-H females. Tumor latency, however, was reduced by 8 months in bitransgenic mice as compared to mice of the other three genotypes. Aneuploidy was frequently observed in tumors from bitransgenic and p53 172R-H mice, but not from mice expressing only the WAP-DES transgene. Expression of IGFBP3 was elevated in tumors from WAP-DES, but not bitransgenic mice, indicating an alteration in the p53/IGF-I axis. These studies indicate that overexpression of des(1-3)hIGF-I increases the frequency of MIN and stochastic mammary tumors and that the appearance of tumors displaying genomic instability is accelerated by mutant p53 172R-H . Oncogene (2000) 19, 889 ± 898.

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Section: Tumorigenesis In the Wap-des Micesupporting

confidence: 85%

Cooperative interaction between mutant p53 and des(1-3)IGF-I accelerates mammary tumorigenesis

et al. 2000

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“…Bax was not detectable in undispersed bursa, but appeared by 30 min after bursal cell dispersion and continued to increase for at least 2 hr. Although Bax was reported to be a transcriptional activation target of p53 (Miyashita and Reed 1995), this induction of Bax with dispersion of bursal cells is probably independent of p53, because p53 pro- tein and mRNA levels are not altered by the dispersion process (Neiman et al 1994a). We conclude that the ratio of Nr13 to Bax decreases dramatically after dispersion of bursal lymphocytes.…”

Section: Induction Of Apoptosis In Bursal Cells By Dispersion Causes mentioning

confidence: 52%

Role of Nr13 in regulation of programmed cell death in the bursa of Fabricius

Lee¹,

Gillet²,

Burnside³

et al. 1999

Genes & Development

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Apoptotic cell death is developmentally regulated in the chicken bursa of Fabricius. Although apoptosis is low in the embryonic bursa, cell death increases markedly after hatching. The expression of Bcl2 family cell death antagonists was examined to identify the genes that regulate bursal cell apoptosis. The expression of Bcl-xL, A1, and Mcl1 was detected in both embryos and hatched birds, whereas Nr13 was expressed at high levels in embryonic bursa, and decreased significantly after hatching, correlating inversely with apoptosis. The oncogene v-reland phorbol myristate acetate, two known inhibitors of bursal cell apoptosis, induced Nr13 expression. Overexpression of Nr13 in DT40 bursal lymphoma cells protected them from low serum-induced apoptosis. The mechanism of inhibition of apoptosis by Nr13 is likely to involve a critical BH4 domain and interaction with death agonist Bax. Deletion of the BH4 domain converted Nr13 into a death agonist. Bax coimmunoprecipitated with Nr13 and Bax was induced, whereas Nr13 levels diminished when bursal lymphoblasts were induced to apoptosis by dispersion. Bursal transplantation studies demonstrated that Nr13 could prevent the in vivo programmed elimination of bursal stem cells after hatching, suggesting that Nr13 plays a role in maintaining bursal stem cells.

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“…p107, p130) or some unknown protein. Apparently normal pRb was detected in DT40 cells; Western blotting of DT40 lysates with a human pRb antibody demonstrated a broad band at ϳ104 kDa, the reported molecular mass for avian pRb (data not shown) (71,72). The inability of the mutant murine cyclin D1, but not the normal murine cyclins D1, D2, and D3, to rescue these D1 Ϫ/Ϫ cells suggests that whatever interacts with the LXCXE motif of cyclin D1, its loss results in an altered cell cycle.…”

Section: Rescue Of the Cyclin D1 ϫ/ϫ Cell Cycle Phenotype By Expressimentioning

confidence: 89%

Elimination of Cyclin D1 in Vertebrate Cells Leads to an Altered Cell Cycle Phenotype, Which Is Rescued by Overexpression of Murine Cyclins D1, D2, or D3 but Not by a Mutant Cyclin D1

Lahti

Kidd

1997

Journal of Biological Chemistry

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DT40 lymphoma B-cells normally express cyclins D1and D2 but not D3. When cyclin D1 expression was extinguished in these cells by gene knockout, specific alterations in their ability to transit the cell cycle were observed. These changes are exemplified by a delay of approximately 2 h in their progression through a normal 14-h cell cycle. This delay results in an increase in the number of cells in the G 2 /M phase population, most likely due to triggering of checkpoints in G 2 /M, inability to enter G 1 normally, and/or alterations of crucial event(s) in early G 1 . The defect(s) in the cell cycle of these D1 "knockout" cells can be rescued by overexpression of any normal mouse D-type cyclin but not by a mutant mouse cyclin D1 protein that lacks the LXCXE motif at its amino terminus. These data suggest that the cell cycle alterations observed in the D1؊/؊ cells are a direct effect of the absence of the cyclin D1 protein and support the hypothesis that the D-type cyclins have separate, but overlapping, functions. Elimination of cyclin D1 also resulted in enhanced sensitivity to radiation, resulting in a significant increase in apoptotic cells. Expression of any normal murine D-type cyclin in the D1؊/؊ cells reversed this phenotype. Intriguingly, expression of the mutant cyclin D1 in the D1 ؊/؊ cells partially restored resistance to radiation-induced apoptosis. Thus, there may be distinct differences in cyclin D1 complexes and/or its target(s) in proliferating and apoptotic DT40 lymphoma B-cells.Regulation of the vertebrate cell cycle requires the periodic formation, activation, and inactivation of unique protein kinase complexes that consist of cyclin (regulatory) and cyclin-dependent kinase (CDK 1 ; catalytic) subunits. Cell cycle-dependent fluctuations in the levels of many of the cyclin proteins are thought to contribute, at least in part, to the activation of these enzymes (1-4). The cyclins are required to regulate many of the p34 cdc2 -related cyclin-dependent protein kinases (CDKs), which have diverse functions prominently linked to the control of cell division (5-16). For example, cyclin B participates in the regulation of the G 2 /M transition by its association with p34 cdc2 , whereas cyclin A appears to be essential for the completion of S phase and entry into G 2 phase in complexes with both p34 cdc2 and cdk2 (17-27). In contrast, complexes formed between the D-type cyclins and both cdk4 and cdk6 integrate growth factor signals and the cell cycle, allowing cells to progress normally through G 1 phase (10, 12, 28 -34). The genetic alterations that occur in this pathway during oncogenesis appear to involve many of its components, including the D-type cyclins, cyclin-dependent protein kinases (cdks), and cyclin-dependent kinase inhibitors (CKIs).Unlike other G 1 cyclins described thus far (e.g. cyclin C and cyclin E), the D-type cyclins are highly homologous to one another and their expression overlaps during G 1 phase, suggesting that this group of cyclins may be somewhat redundant in their function. How...

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Loss of cell cycle controls in apoptotic lymphoblasts of the bursa of Fabricius.

Cited by 13 publications

References 35 publications

Cooperative interaction between mutant p53 and des(1-3)IGF-I accelerates mammary tumorigenesis

Cooperative interaction between mutant p53 and des(1-3)IGF-I accelerates mammary tumorigenesis

Role of Nr13 in regulation of programmed cell death in the bursa of Fabricius

Elimination of Cyclin D1 in Vertebrate Cells Leads to an Altered Cell Cycle Phenotype, Which Is Rescued by Overexpression of Murine Cyclins D1, D2, or D3 but Not by a Mutant Cyclin D1

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