Previously, rLZ-8 has been shown to exert immunomodulation activity
on cells involved in various immune responses (8,13,15). However, this
protein’s effect on the growth of tumors has not been properly explored.
Here, we have demonstrated that rLZ-8 exhibits an anticancer growth
effect both in vitro and in vivo via p53-dependent G1 arrest. This
p53-dependent arrest is probably due to a perturbation of ribosome
biogenesis, which is presumably induced by rLZ-8 and results in the
interaction of MDM2 with S7 and the stabilization of p53. Nevertheless,
how rLZ-8 exerts an effect that perturbs ribosome biogenesis
remains to be explored.
The biogenesis of ribosomes is a highly co-ordinated process that
involves the synthesis and process of ribosomal RNA, the production of
RPs and the assembly of ribosomal subunits. Importantly, this process
is tightly linked to cell growth and proliferation including in cancer
cells (38), and upregulation of rRNA has been correlated with uncontrolled
growth in cancer cells (39–41). We have shown that rLZ-8
reduces pre-rRNA expression, which suggests that rLZ-8 may affect
pathways associated with either RNA polymerase I activity or the
various transcriptional factors that are involved in rRNA transcription
(21,41). Since p53 regulates the transcription of many genes including
rRNA (42), we hypothesize that one possibility is that rLZ-8 activated
p53 may directly regulate the transcription of rRNA. Moreover, from
the results of the polysome study, rLZ-8 may also affect the assembly of
either the 40S or 60S ribosome subunits or, alternatively, the assembly
of polysomes.
It is well known that various stresses can activate p53 thro
Previously, rLZ-8 has been shown to exert immunomodulation activityon cells involved in various immune responses (8,13,15). However, thisprotein’s effect on the growth of tumors has not been properly explored.Here, we have demonstrated that rLZ-8 exhibits an anticancer growtheffect both in vitro and in vivo via p53-dependent G1 arrest. Thisp53-dependent arrest is probably due to a perturbation of ribosomebiogenesis, which is presumably induced by rLZ-8 and results in theinteraction of MDM2 with S7 and the stabilization of p53. Nevertheless,how rLZ-8 exerts an effect that perturbs ribosome biogenesisremains to be explored.The biogenesis of ribosomes is a highly co-ordinated process thatinvolves the synthesis and process of ribosomal RNA, the production ofRPs and the assembly of ribosomal subunits. Importantly, this processis tightly linked to cell growth and proliferation including in cancercells (38), and upregulation of rRNA has been correlated with uncontrolledgrowth in cancer cells (39–41). We have shown that rLZ-8reduces pre-rRNA expression, which suggests that rLZ-8 may affectpathways associated with either RNA polymerase I activity or thevarious transcriptional factors that are involved in rRNA transcription(21,41). Since p53 regulates the transcription of many genes includingrRNA (42), we hypothesize that one possibility is that rLZ-8 activatedp53 may directly regulate the transcription of rRNA. Moreover, fromthe results of the polysome study, rLZ-8 may also affect the assembly ofeither the 40S or 60S ribosome subunits or, alternatively, the assemblyof polysomes.It is well known that various stresses can activate p53 thro
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