IL-4 inhibits proliferation of renal carcinoma cells by increasing the expression of p21WAF1 and IRF-1

Yu, Sora; Kim, Hyeon Soo; Cho, Sung Won; Sohn, Jeongwon

doi:10.1038/emm.2004.49

Cited by 21 publications

(14 citation statements)

References 22 publications

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“…Experiments using siRNA and macrophages from p21 Waf1 KO mice demonstrated that p21 Waf1 is the key molecule induced by IL-4 to block proliferation. These results are in agreement with previous studies, which showed that the antiproliferative role of IL-4 is mediated by p21 Waf1 [46]. The role of…”

Section: Arginase1supporting

confidence: 94%

IL‐4 blocks M‐CSF‐dependent macrophage proliferation by inducing p21^Waf1 in a STAT6‐dependent way

2009

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Macrophages are recruited from the blood stream to the inflammatory loci to carry out their functional activities. In an early phase of the cell cycle, macrophages become activated by Th1-type cytokines (i.e. IFN-c), thereby producing several factors (cytokines, NO, etc.) and developing pro-inflammatory activities. When bacteria and apoptotic bodies are removed, through the interaction with Th2-type cytokines (i.e. IL-4), macrophages become anti-inflammatory and repair damaged tissues. Incubation of bone-marrow-derived macrophages with IFN-c or IL-4 blocked their proliferation. While M-CSF withdrawal caused cell cycle arrest at the early G 1 phase , treatment of macrophages with IFN-c or IL-4 caused this arrest later, at the G 1 /S boundary. Proliferation arrest was not due to an induction of apoptosis. IFN-c and IL-4 induced the expression of the cyclin-dependent kinase (Cdk) inhibitor p21 Waf1. Using KO mice and iRNA experiments, we found that p21Waf1 is required for IL-4-but not for IFN-c-dependent inhibition of macrophage proliferation. IL-4 inhibited M-CSF-dependent Cdk-2 and Cdk-4 activities, which are necessary for entry and passage through the S phase of the cell cycle. The signal transduction used to induce the expression of p21 Waf1 after interaction of IL-4 with the corresponding receptor was mediated by STAT6. Thus, IL-4 and IFN-c blocked M-CSF-induced macrophage proliferation through distinct mechanisms.

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Section: Arginase1supporting

confidence: 94%

IL‐4 blocks M‐CSF‐dependent macrophage proliferation by inducing p21^Waf1 in a STAT6‐dependent way

2009

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“…In the kidney, Ortmann et al (2004) observed that an improvement of structural injury in glomeruli and podocytes was accompanied by a reduction of the expression of p21 waf1/cip1 . In renal tumor cells (Caki-1) p21 waf1/cip1 upregulation has been described as pro-apoptotic mechanism targeted by different reagents such as monensin (Park et al, 2003), phenylacetate (Franco et al, 2003), and interleukin-4 (Yu et al, 2004). Gene regulation of p21 waf1/cip1 is mediated by the direct binding of p53 to two highly conserved p53-response elements.…”

Section: Introductionmentioning

confidence: 98%

ETS-dependent p16INK4a and p21waf1/cip1 gene expression upon endothelin-1 stimulation in malignant versus and non-malignant proximal tubule cells

et al. 2012

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“…Immunoblot analysis was carried out as previously described (53). Briefly, total cell lysates (30 g) were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred onto a nitrocellulose membrane.…”

Section: Methodsmentioning

confidence: 99%

Glycogen Synthase Kinase 3β Phosphorylates p21^WAF1/CIP1 for Proteasomal Degradation after UV Irradiation

Lee

Park

et al. 2007

Molecular and Cellular Biology

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UV irradiation has been reported to induce p21WAF1/CIP1 protein degradation through a ubiquitinproteasome pathway, but the underlying biochemical mechanism remains to be elucidated. Here, we show that ser-114 phosphorylation of p21 protein by glycogen synthase kinase 3␤ (GSK-3␤) is required for its degradation in response to UV irradiation and that GSK-3␤ activation is a downstream event in the ATR signaling pathway triggered by UV. UV transiently increased GSK-3␤ activity, and this increase could be blocked by caffeine or by ATR small interfering RNA, indicating ATR-dependent activation of GSK-3␤. ser-114, located within the putative GSK-3␤ target sequence, was phosphorylated by GSK-3␤ upon UV exposure. The nonphosphorylatable S114A mutant of p21 was protected from UV-induced destabilization. Degradation of p21 protein by UV irradiation was independent of p53 status and prevented by proteasome inhibitors. In contrast to the previous report, the proteasomal degradation of p21 appeared to be ubiquitination independent. These data show that GSK-3␤ is activated by UV irradiation through the ATR signaling pathway and phosphorylates p21 at ser-114 for its degradation by the proteasome. To our knowledge, this is the first demonstration of GSK-3␤ as the missing link between UV-induced ATR activation and p21 degradation.

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IL-4 inhibits proliferation of renal carcinoma cells by increasing the expression of p21WAF1 and IRF-1

Cited by 21 publications

References 22 publications

IL‐4 blocks M‐CSF‐dependent macrophage proliferation by inducing p21^Waf1 in a STAT6‐dependent way

IL‐4 blocks M‐CSF‐dependent macrophage proliferation by inducing p21^Waf1 in a STAT6‐dependent way

ETS-dependent p16INK4a and p21waf1/cip1 gene expression upon endothelin-1 stimulation in malignant versus and non-malignant proximal tubule cells

Glycogen Synthase Kinase 3β Phosphorylates p21^WAF1/CIP1 for Proteasomal Degradation after UV Irradiation

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IL-4 inhibits proliferation of renal carcinoma cells by increasing the expression of p21WAF1 and IRF-1

Cited by 21 publications

References 22 publications

IL‐4 blocks M‐CSF‐dependent macrophage proliferation by inducing p21Waf1 in a STAT6‐dependent way

IL‐4 blocks M‐CSF‐dependent macrophage proliferation by inducing p21Waf1 in a STAT6‐dependent way

ETS-dependent p16INK4a and p21waf1/cip1 gene expression upon endothelin-1 stimulation in malignant versus and non-malignant proximal tubule cells

Glycogen Synthase Kinase 3β Phosphorylates p21WAF1/CIP1 for Proteasomal Degradation after UV Irradiation

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IL‐4 blocks M‐CSF‐dependent macrophage proliferation by inducing p21^Waf1 in a STAT6‐dependent way

IL‐4 blocks M‐CSF‐dependent macrophage proliferation by inducing p21^Waf1 in a STAT6‐dependent way

Glycogen Synthase Kinase 3β Phosphorylates p21^WAF1/CIP1 for Proteasomal Degradation after UV Irradiation