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A role for antizyme inhibitor in cell proliferation.

Silva, Tania LU ; Cirenajwis, Helena LU ; Wallace, Heather M; Oredsson, Stina and Persson, Lo LU (2015) In Amino Acids 47(7). p.1341-1352
Abstract
The polyamines are important for a variety of cellular functions, including cell growth. Their intracellular concentrations are controlled by a complex network of regulatory mechanisms, in which antizyme (Az) has a key role. Az reduces the cellular polyamine content by down-regulating both the enzyme catalysing polyamine biosynthesis, ornithine decarboxylase (ODC), and the uptake of polyamines. The activity of Az is repressed by the binding of a protein, named Az inhibitor (AzI), which is an enzymatically inactive homologue of ODC. Two forms of AzI have been described: AzI1, which is ubiquitous, and AzI2 which is expressed in brain and testis. In the present study, we have investigated the role of AzI1 in polyamine homeostasis and cell... (More)
The polyamines are important for a variety of cellular functions, including cell growth. Their intracellular concentrations are controlled by a complex network of regulatory mechanisms, in which antizyme (Az) has a key role. Az reduces the cellular polyamine content by down-regulating both the enzyme catalysing polyamine biosynthesis, ornithine decarboxylase (ODC), and the uptake of polyamines. The activity of Az is repressed by the binding of a protein, named Az inhibitor (AzI), which is an enzymatically inactive homologue of ODC. Two forms of AzI have been described: AzI1, which is ubiquitous, and AzI2 which is expressed in brain and testis. In the present study, we have investigated the role of AzI1 in polyamine homeostasis and cell proliferation in breast cancer cells. The results obtained showed that the cellular content of AzI increased transiently after induction of cell proliferation by diluting cells in fresh medium. Inhibition of polyamine biosynthesis induced an even larger increase in the cellular AzI content, which remained significantly elevated during the 7-day experimental period. However, this increase was not a consequence of changes in cell cycle progression, as demonstrated by flow cytometry. Instead, the increase appeared to correlate with the cellular depletion of polyamines. Moreover, induced overexpression of AzI resulted in an increased cell proliferation with a concomitant increase in ODC activity and putrescine content. During mitosis, AzI1 was localised in a pattern that resembled that of the two centrosomes, confirming earlier observations. Taken together, the results indicate that AzI fulfils an essential regulatory function in polyamine homeostasis and cell proliferation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Amino Acids
volume
47
issue
7
pages
1341 - 1352
publisher
Springer
external identifiers
  • pmid:25813938
  • wos:000355745900005
  • scopus:84930536584
ISSN
0939-4451
DOI
10.1007/s00726-015-1957-6
language
English
LU publication?
yes
id
8eb5643a-a043-4720-b2cc-57bbf87ef6d4 (old id 5257569)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25813938?dopt=Abstract
date added to LUP
2015-04-04 17:22:53
date last changed
2017-04-30 05:44:25
@article{8eb5643a-a043-4720-b2cc-57bbf87ef6d4,
  abstract     = {The polyamines are important for a variety of cellular functions, including cell growth. Their intracellular concentrations are controlled by a complex network of regulatory mechanisms, in which antizyme (Az) has a key role. Az reduces the cellular polyamine content by down-regulating both the enzyme catalysing polyamine biosynthesis, ornithine decarboxylase (ODC), and the uptake of polyamines. The activity of Az is repressed by the binding of a protein, named Az inhibitor (AzI), which is an enzymatically inactive homologue of ODC. Two forms of AzI have been described: AzI1, which is ubiquitous, and AzI2 which is expressed in brain and testis. In the present study, we have investigated the role of AzI1 in polyamine homeostasis and cell proliferation in breast cancer cells. The results obtained showed that the cellular content of AzI increased transiently after induction of cell proliferation by diluting cells in fresh medium. Inhibition of polyamine biosynthesis induced an even larger increase in the cellular AzI content, which remained significantly elevated during the 7-day experimental period. However, this increase was not a consequence of changes in cell cycle progression, as demonstrated by flow cytometry. Instead, the increase appeared to correlate with the cellular depletion of polyamines. Moreover, induced overexpression of AzI resulted in an increased cell proliferation with a concomitant increase in ODC activity and putrescine content. During mitosis, AzI1 was localised in a pattern that resembled that of the two centrosomes, confirming earlier observations. Taken together, the results indicate that AzI fulfils an essential regulatory function in polyamine homeostasis and cell proliferation.},
  author       = {Silva, Tania and Cirenajwis, Helena and Wallace, Heather M and Oredsson, Stina and Persson, Lo},
  issn         = {0939-4451},
  language     = {eng},
  number       = {7},
  pages        = {1341--1352},
  publisher    = {Springer},
  series       = {Amino Acids},
  title        = {A role for antizyme inhibitor in cell proliferation.},
  url          = {http://dx.doi.org/10.1007/s00726-015-1957-6},
  volume       = {47},
  year         = {2015},
}