p53-Independent Elevation of p21 Expression by PMA Results from PKC-Mediated mRNA Stabilization

Park, Jong‐Wook; Jang, Min-Ah; Lee, Young Han; Passaniti, Antonino; Kwon, Taeg Kyu

doi:10.1006/bbrc.2000.4105

Cited by 42 publications

(29 citation statements)

References 23 publications

(19 reference statements)

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“…p38 has been identified as an essential kinase in Page 20 of 48 A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 20 regulating IL-1β-mediated mRNA stabilization in multiple studies [12, 15-17, 41-44, 56], of which several have specifically investigated IL-1β-mediated COX-2 and IL-6 mRNA stabilization. On the other hand, PKC has been implicated in the stabilization of a variety of other mRNAs such as, p21, GAP-43 and IL-1β itself [19,20,22,23]. Importantly, PKC has been convincingly implicated in COX-2 mRNA stabilization in several recent studies [21,31,44,54,68] and, indirectly, in IL-6 mRNA stabilization in one older study [69].…”

Section: Discussionmentioning

confidence: 98%

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IL-1β potently stabilizes IL-6 mRNA in human astrocytes

Spooren

Mestdagh

Rondou

et al. 2011

Biochemical Pharmacology

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Uncontrolled expression of IL-6 in the central nervous system is associated with neurodegenerative pathology and glioma development. Astrocytes are the predominant source of IL-6 in the central nervous system, and they are characteristically susceptible to synergistic IL-6 expression. Combined β-adrenergic and TNF-receptor triggering induces synergistic IL-6 expression in 1321N1 cells via a transcriptional enhancer mechanism. Here, we have investigated the molecular basis of the very potent "super"-synergistic IL-6 expression that is apparent after combined treatment of astrocytes with a β-adrenergic agonist, isoproterenol, and the inflammatory cytokines TNF-α and IL-1β. We found that IL-1β treatment strengthens the IL-6 synergy by inducing a distinct stabilization of IL-6 mRNA. Surprisingly, the mRNAstabilizing effect seems to be dependent on protein kinase C (PKC), but not on the prototypical mRNA-stabilizing kinase p38. Moreover, although the mRNA-binding protein HuR basally stabilizes IL-6 mRNA, the mRNA-stabilizing effect of IL-1β is independent of HuR. Our data using pharmacological inhibitors suggest PKC is an important modulator of IL-6 expression in the central nervous system and this might have therapeutic implications.

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Section: Discussionmentioning

confidence: 98%

“…Another kinase often associated with mRNA stabilization is protein kinase C (PKC). PKC activation has been implicated in mRNA stabilization of, among others, GAP-43 [19,20], COX-2 [21], IL-1β [22] and p21 [23]. Moreover, PKC and p38 target several RNA-binding proteins that bind 3"UTRs and stabilize or destabilize the mRNA.…”

Section: Page 4 Of 48mentioning

confidence: 99%

IL-1β potently stabilizes IL-6 mRNA in human astrocytes

Spooren

Mestdagh

Rondou

et al. 2011

Biochemical Pharmacology

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“…Cip1 is controlled both by transcriptional and posttranscriptional mechanisms, including in response to PMA (4,32,33). Previous studies from our laboratory established a key role for PKC␦ in p21…”

Section: Rock Regulates P21 Cip1 At a Transcriptional Level-expressiomentioning

confidence: 94%

“…This induction could be either p53-dependent or p53-independent, depending upon the cell type and stimuli (4,32,33). Studies have shown that p21…”

Section: Rock-mediated P21mentioning

confidence: 99%

ROCK Mediates Phorbol Ester-induced Apoptosis in Prostate Cancer Cells via p21Cip1 Up-regulation and JNK

Xiao

Eto

Kazanietz

2009

Journal of Biological Chemistry

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“…Although, the p21 Cip1/WAF1 gene was first identified as a p53-inducible gene, more recently its induction was shown to occur via p53-independent mechanisms in various cell lines stimulated for differentiation and growth arrest, including thyroid carcinoma cells (Park et al 2001). The p53 tumor suppressor gene is mutated in about half of most types of cancer arising from a wide spectrum of tissues (Bourdon 2007).…”

Section: Bonofiglio H Qi Et Al: Pparg Regulates P21mentioning

confidence: 99%

Peroxisome proliferator-activated receptor inhibits follicular and anaplastic thyroid carcinoma cells growth by upregulating p21Cip1/WAF1 gene in a Sp1-dependent manner

Bonofiglio¹,

Qi²,

Gabriele³

et al. 2008

Endocrine Related Cancer

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Peroxisome proliferator-activated receptor g (PPARg) has been demonstrated to be antineoplastic against various human tumors. The aim of this study was to delineate the molecular mechanism underlying PPARg ligand rosiglitazone (BRL) antiproliferative effects in follicular WRO and anaplastic FRO human thyroid carcinoma cells. BRL upregulated the p21Cip1/WAF1 levels in the two thyroid cancer cells, while did not modify the p53 protein content. Different evidences indicate that the p21 Cip1/WAF1 upregulation by BRL requires a functional PPARg, since it was reversed by silencing PPARg and pretreatment with GW9662, an irreversible PPARg antagonist. Transient transfection assays showed that BRL triggered the transcriptional activity of p21Cip1/WAF1 promoter gene in a p53-independent way, being a p21 Cip1/WAF1 promoter construct deleted in the p53 sites still activated by BRL. The Sp1 inhibitor mithramycin silenced the p21 Cip1/WAF1 promoter activity suggesting an important role of Sp1 in mediating BRL activation. The electrophoretic mobility shift and chromatin immunoprecipitation (ChIP) assays evidenced a functional interaction between PPARg and Sp1 in regulating p21Cip1/WAF1 . Intriguingly, ChIP analysis revealed in the p21 Cip1/WAF1 gene promoter an increased recruitment of the RNA Pol II associated with an increased histone H3 acetylation and a reduced H3 methylation. The biological event, consistent with PPARg-induced WRO and FRO cell growth inhibition, was reversed by p21Cip1/WAF1 antisense oligonucleotides and was confirmed by increasing the PPARg expression, suggesting a crucial role exerted by p21Cip1/WAF1 in PPARg action. Our results further candidate BRL as a potential agent able to inhibit tumor progression of follicular and anaplastic thyroid carcinoma.

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p53-Independent Elevation of p21 Expression by PMA Results from PKC-Mediated mRNA Stabilization

Cited by 42 publications

References 23 publications

IL-1β potently stabilizes IL-6 mRNA in human astrocytes

IL-1β potently stabilizes IL-6 mRNA in human astrocytes

ROCK Mediates Phorbol Ester-induced Apoptosis in Prostate Cancer Cells via p21Cip1 Up-regulation and JNK

Peroxisome proliferator-activated receptor inhibits follicular and anaplastic thyroid carcinoma cells growth by upregulating p21Cip1/WAF1 gene in a Sp1-dependent manner

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