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A role for antizyme inhibitor in cell proliferation
#MMPMID25813938
Silva TM
; Cirenajwis H
; Wallace HM
; Oredsson S
; Persson L
Amino Acids
2015[Jul]; 47
(7
): 1341-52
PMID25813938
show ga
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.
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