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PIM1 kinase is destabilized by ribosomal stress causing inhibition of cell cycle progression

Iadevaia, V.; Caldarola, S.; Biondini, L.; Gismondi, A.; Karlsson, Stefan LU ; Dianzani, I. and Loreni, F. (2010) In Oncogene 29(40). p.5490-5499
Abstract
PIM1 is a constitutively active serine/threonine kinase regulated by cytokines, growth factors and hormones. It has been implicated in the control of cell cycle progression and apoptosis and its overexpression has been associated with various kinds of lymphoid and hematopoietic malignancies. The activity of PIM1 is dependent on the phosphorylation of several targets involved in transcription, cell cycle and apoptosis. We have recently observed that PIM1 interacts with ribosomal protein (RP) S19 and cosediments with ribosomes. Defects in ribosome synthesis (ribosomal stress) have been shown to activate a p53-dependent growth arrest response. To investigate if PIM1 could have a role in the response to ribosomal stress, we induced ribosome... (More)
PIM1 is a constitutively active serine/threonine kinase regulated by cytokines, growth factors and hormones. It has been implicated in the control of cell cycle progression and apoptosis and its overexpression has been associated with various kinds of lymphoid and hematopoietic malignancies. The activity of PIM1 is dependent on the phosphorylation of several targets involved in transcription, cell cycle and apoptosis. We have recently observed that PIM1 interacts with ribosomal protein (RP) S19 and cosediments with ribosomes. Defects in ribosome synthesis (ribosomal stress) have been shown to activate a p53-dependent growth arrest response. To investigate if PIM1 could have a role in the response to ribosomal stress, we induced ribosome synthesis alterations in TF-1 and K562 erythroid cell lines. We found that RP deficiency, induced by RNA interference or treatment with inhibitor of nucleolar functions, causes a drastic destabilization of PIM1. The lower level of PIM1 induces an increase in the cell cycle inhibitor p27(Kip1) and blocks cell proliferation even in the absence of p53. Notably, restoring PIM1 level by transfection causes a recovery of cell growth. Our data indicate that PIM1 may act as a sensor for ribosomal stress independently of or in concert with the known p53-dependent mechanisms. Oncogene (2010) 29, 5490-5499; doi:10.1038/onc.2010.279; published online 19 July 2010 (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
erythroleukemia cells, ribosome synthesis, cell cycle arrest, PIM1, RPS19, p27(Kip1)
in
Oncogene
volume
29
issue
40
pages
5490 - 5499
publisher
Nature Publishing Group
external identifiers
  • wos:000282945800006
  • scopus:77957757746
ISSN
1476-5594
DOI
10.1038/onc.2010.279
language
English
LU publication?
yes
id
2eb96e32-72fd-443c-8666-0de3c2064318 (old id 1725563)
date added to LUP
2010-12-03 12:19:56
date last changed
2018-05-29 10:37:23
@article{2eb96e32-72fd-443c-8666-0de3c2064318,
  abstract     = {PIM1 is a constitutively active serine/threonine kinase regulated by cytokines, growth factors and hormones. It has been implicated in the control of cell cycle progression and apoptosis and its overexpression has been associated with various kinds of lymphoid and hematopoietic malignancies. The activity of PIM1 is dependent on the phosphorylation of several targets involved in transcription, cell cycle and apoptosis. We have recently observed that PIM1 interacts with ribosomal protein (RP) S19 and cosediments with ribosomes. Defects in ribosome synthesis (ribosomal stress) have been shown to activate a p53-dependent growth arrest response. To investigate if PIM1 could have a role in the response to ribosomal stress, we induced ribosome synthesis alterations in TF-1 and K562 erythroid cell lines. We found that RP deficiency, induced by RNA interference or treatment with inhibitor of nucleolar functions, causes a drastic destabilization of PIM1. The lower level of PIM1 induces an increase in the cell cycle inhibitor p27(Kip1) and blocks cell proliferation even in the absence of p53. Notably, restoring PIM1 level by transfection causes a recovery of cell growth. Our data indicate that PIM1 may act as a sensor for ribosomal stress independently of or in concert with the known p53-dependent mechanisms. Oncogene (2010) 29, 5490-5499; doi:10.1038/onc.2010.279; published online 19 July 2010},
  author       = {Iadevaia, V. and Caldarola, S. and Biondini, L. and Gismondi, A. and Karlsson, Stefan and Dianzani, I. and Loreni, F.},
  issn         = {1476-5594},
  keyword      = {erythroleukemia cells,ribosome synthesis,cell cycle arrest,PIM1,RPS19,p27(Kip1)},
  language     = {eng},
  number       = {40},
  pages        = {5490--5499},
  publisher    = {Nature Publishing Group},
  series       = {Oncogene},
  title        = {PIM1 kinase is destabilized by ribosomal stress causing inhibition of cell cycle progression},
  url          = {http://dx.doi.org/10.1038/onc.2010.279},
  volume       = {29},
  year         = {2010},
}