Predisposition to lymphomagenesis in pim-1 transgenic mice: Cooperation with c-myc and N-myc in murine leukemia virus-induced tumors

Lohuizen, Maarten van; Verbeek, Sjef; Krimpenfort, Paul; Domen, Jos; Saris, Christiaan J. M.; Radaszkiewicz, T; Berns, Anton

doi:10.1016/0092-8674(89)90589-8

Cited by 473 publications

(409 citation statements)

References 34 publications

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“…Cross-breeding with animals transgenic for Em-pim-1, a gene known to cooperate with c-myc in murine lymphomagenesis (van Lohuizen et al, 1989), led to an acceleration of disease onset. Nonetheless, the predilection toward the development of T cell neoplasia was maintained.…”

Section: E Ects Of Myc Gene Gain-and Loss-of-function In Vivomentioning

confidence: 99%

MYC oncogenes and human neoplastic disease

1999

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c-myc, N-myc and L-myc are the three members of the myc oncoprotein family whose role in the pathogenesis of many human neoplastic diseases has received wide empirical support. In this review, we ®rst summarize data, derived mainly from non-clinical studies, indicating that these oncoproteins actually serve quite di erent roles in vivo. This concept necessarily lies at the heart of the basis for the observation that the deregulated expression of each MYC gene is reproducibly associated with only certain naturally occurring malignancies in humans and that these genes are not interchangeable with respect to their aberrant functional consequences. We also review evidence implicating each of the above MYC genes in speci®c neoplastic diseases and have attempted to identify unresolved questions which deserve further basic or clinical investigation. We have made every attempt to review those diseases for which signi®cant and con®rmatory evidence, based on studies with primary tumor material, exists to implicate MYC members in their causation and/or progression.

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Section: E Ects Of Myc Gene Gain-and Loss-of-function In Vivomentioning

confidence: 99%

MYC oncogenes and human neoplastic disease

1999

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“…Besides interacting with EBNA2 and Myb, p100 was also identi®ed in a yeast two-hybrid screen as a protein that interacted with the serine/threonine protein kinase Pim-1 . The Pim-1 kinase is encoded by an oncogene that can operate with activated alleles of c-myc to induce murine lymphoid tumors (van Lohuizen et al, 1989). Pim-1 is expressed in immature hematopoietic cells, the same cells that express c-Myb (for review see Ihle et al, 1990), and its expression is regulated by STAT-factor mediated signaling cascades downstream of hematopoietic cytokine receptors (Miura et al, 1994).…”

Section: Cbp and P300mentioning

confidence: 99%

Myb binding proteins: regulators and cohorts in transformation

Ness

1999

Oncogene

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The c-Myb and v-Myb proteins are transcription factors that regulate cell proliferation and di erentiation. Both Myb proteins have been shown to interact with a number of cellular proteins, some of which are transcription factors that cooperate to activate speci®c promoters, while others regulate the transcriptional activity of Myb in speci®c contexts. By comparing and analysing the types of proteins that bind Myb, and the conserved domains of Myb that interact with other proteins, conclusions can be drawn regarding the role of speci®c partner proteins in the regulation of gene expression, cell proliferation and disease.

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“…The Pim proteins have been implicated in the control of tumorigenesis, cell cycle progression and apoptosis (Wang et al, 2001;Mikkers et al, 2004;Amaravadi and Thompson, 2005;Bachmann and Moroy, 2005). In animal models, Pim protein kinases have been shown to enhance development of lymphoma induced by c-Myc, and to be overexpressed in hepatocellular cancer (Cuypers et al, 1984;Selten et al, 1985;van Lohuizen et al, 1989). In humans, the protein levels of Pim have been shown to be elevated in lymphomas (Ionov et al, 2003), leukemias (Adam et al, 2006) and prostate cancer (Cibull et al, 2006;Xu et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Negative regulation of Pim-1 protein kinase levels by the B56β subunit of PP2A

Arnold

Lilly

et al. 2007

Oncogene

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The Pim protein kinases are serine threonine protein kinases that regulate important cellular signaling pathway molecules, and enhance the ability of c-Myc to induce lymphomas. We demonstrate that a cascade of events controls the cellular levels of Pim. We find that overexpression of the protein phosphatase (PP) 2A catalytic subunit decreases the activity and protein levels of Pim-1. This effect is reversed by the application of okadaic acid, an inhibitor of PP2A, and is blocked by SV40 small T antigen that is known to disrupt B subunit binding to PP2A A and C subunits. Pim-1 can coimmunoprecipitate with the PP2A regulatory B subunit, B56b, but not B56a, c, d, e or B55a. Using short hairpin RNA targeted at B56b, we demonstrate that decreasing the level of B56b increases the half-life of Pim-1 from 0.7 to 2.8 h, and decreases the ubiquitinylation level of Pim-1. We also find that Pin1, a prolyl-isomerase, is capable of binding Pim-1 and leads to a decrease in the protein level of Pim-1. On the basis of these observations, we hypothesize that phosphorylated Pim-1 binds Pin1 allowing the interaction of PP2A through B56b. Dephosphorylation of Pim-1 then allows for ubiquitinylation and protein degradation of Pim-1.

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Predisposition to lymphomagenesis in pim-1 transgenic mice: Cooperation with c-myc and N-myc in murine leukemia virus-induced tumors

Cited by 473 publications

References 34 publications

MYC oncogenes and human neoplastic disease

MYC oncogenes and human neoplastic disease

Myb binding proteins: regulators and cohorts in transformation

Negative regulation of Pim-1 protein kinase levels by the B56β subunit of PP2A

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