Collaboration of PIM-1 and BCL-2 in Lymphomagenesis

Acton, D; Domen, Jos; Jacobs, Heinz; Vlaar, M.; Korsmeyer, Stanley J.; Berns, Anton

doi:10.1007/978-3-642-77633-5_36

Cited by 41 publications

(57 citation statements)

References 10 publications

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“…Overexpression of these proteins greatly increases the clonogenic survival of at least some tumour cells (Strasser et al, 1994a) and deregulated expression of bcl-2 is lymphomagenic (McDonnell and Korsmeyer, 1991;Strasser et al, 1993;Linette et al, 1995), especially in conjunction with overexpression of proto-oncogenes that promote cell proliferation, such as c-myc and pim-1 (Strasser et al, 1990;Acton et al, 1992). The development of an antagonist capable of inhibiting all functional homologues of Bcl-2 and thereby enhancing sensitivity to apoptosis therefore holds great promise for the treatment of neoplastic disease, particularly in combination with other therapeutic regimes.…”

Section: Discussionmentioning

confidence: 99%

Bcl-2, Bcl-xL and adenovirus protein E1B19kD are functionally equivalent in their ability to inhibit cell death

1997

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Section: Discussionmentioning

confidence: 99%

Bcl-2, Bcl-xL and adenovirus protein E1B19kD are functionally equivalent in their ability to inhibit cell death

1997

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“…The capacity of pim-1 and myc to synergize in lymphomagenesis was most convincingly shown with crosses of Em-pim-1 and Em-myc transgenic mice which resulted in development of lymphoid malignancies already in utero (MoÈ roÈ y et al, 1991;Verbeek et al, 1991). pim-1 has been shown to cooperate in lymphomagenesis also with bcl-2 (Acton et al, 1992), suggesting that overexpression of pim-1 can enhance or complement the e ects of two types of oncogenes that either promote cell proliferation (myc) or cell survival (bcl-2). While the mechanisms of oncogene cooperation still remain unclear, experimental evidence indicates that Pim-1 can enhance the activity of some transcription factors such as c-Myb (Leverson et al, 1998) and NFATc1 (EM Rainio, J Sandholm and PJ Koskinen, in preparation).…”

Section: Introductionmentioning

confidence: 99%

Developmental expression of Pim kinases suggests functions also outside of the hematopoietic system

et al. 2000

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We have cloned a novel quail cDNA with strong homology to the pim family of proto-oncogenes. The deduced amino acid (aa) sequence of the cDNA, named qpim, is more closely related to Xenopus Pim and to the recently identi®ed rat Pim-3 than to human or rodent Pim-1 or Pim-2. The protein encoded by the qpim cDNA can autophosphorylate itself and share substrates with murine Pim-1, suggesting functional redundancy to other Pim family serine/threonine kinases. We have compared the expression of qpim in avian embryos to mouse pim-1, -2 and -3 by in situ hybridization. qpim shows a highly dynamic expression pattern, particularly at early developmental stages. Surprisingly, its expression pattern is not identical to any of the murine pim genes, which show complementary and/or partially overlapping expression sites both in-and outside of the hematopoietic system. Altogether, our results suggest novel functions for Pim family kinases during embryonic development, in particular in epithelia and in the central nervous system.

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“…Based on this idea, one could clearly understand why Pim-1 cooperates with c-Myc both in apoptosis and transformation. Moreover, it provides a better explanation for the recent observation that Bcl-2 cooperates with Pim-1 in lymphomagenesis in transgenic mice (Acton et al, 1992). If one assumes that Pim-1 contributes to lymphomagenesis solely by inhibiting apoptosis, it would be rather di cult to understand why Pim-1 should so e ciently cooperate with an antiapoptotic protein Bcl-2 to transform cells.…”

Section: Discussionmentioning

confidence: 97%

Pim-1 kinase stimulates c-Myc-mediated death signaling upstream of caspase-3 (CPP32)-like protease activation

Mochizuki¹,

Kitanaka²,

Noguchi³

et al. 1997

Oncogene

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Pim-1 oncoprotein is a serine/threonine kinase that can closely cooperate with c-Myc in lymphomagenesis, as does Bcl-2. Although the molecular mechanism of this cooperative transformation remains unknown, it is speculated that, similar to Bcl-2, Pim-1 contributes to transformation by inhibiting apoptosis. In this study, therefore, we examined the e ect of Pim-1 expression on c-Myc-mediated apoptosis of Rat-1 ®broblasts triggered by serum deprivation. Our results showed that, rather than inhibiting apoptosis, Pim-1 expression stimulated cMyc-mediated apoptosis in Rat-1 ®broblasts. Pim-1 stimulated c-Myc-mediated apoptosis through an enhancement of the c-Myc-mediated activation of caspase-3 (CPP32)-like proteases, since the suppression of this activity by a speci®c caspase inhibitor abolished the apoptosis stimulation by Pim-1. A kinase-defective Pim-1 mutant failed to stimulate c-Myc-mediated apoptosis, and Pim-1 expression alone in the absence of c-Myc overexpression did not induce apoptosis of serumdeprived Rat-1 cells, indicating that the kinase activity of Pim-1 and the activated c-Myc signaling pathway were required for apoptosis stimulation by Pim-1. Together, these results suggest that Pim-1 oncoprotein stimulates as a serine/threonine kinase the death signaling elicited by c-Myc at a step upstream of caspase-3-like protease activation in Rat-1 ®broblasts. Our results also suggest that Pim-1 kinase might function cooperatively with c-Myc through the phosphorylation of a factor(s) which regulates the common signaling pathway involved in c-Myc-mediated apoptosis and transformation.

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Collaboration of PIM-1 and BCL-2 in Lymphomagenesis

Cited by 41 publications

References 10 publications

Bcl-2, Bcl-xL and adenovirus protein E1B19kD are functionally equivalent in their ability to inhibit cell death

Bcl-2, Bcl-xL and adenovirus protein E1B19kD are functionally equivalent in their ability to inhibit cell death

Developmental expression of Pim kinases suggests functions also outside of the hematopoietic system

Pim-1 kinase stimulates c-Myc-mediated death signaling upstream of caspase-3 (CPP32)-like protease activation

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