scholarly journals The RNA-Binding Protein PCBP1 Functions as a Tumor Suppressor in Prostate Cancer by Inhibiting Mitogen Activated Protein Kinase 1

2018 ◽  
Vol 48 (4) ◽  
pp. 1747-1754 ◽  
Author(s):  
Yingying Zhang ◽  
Lin Meng ◽  
Lin Xiao ◽  
Ruiwang Liu ◽  
Zhonghai Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Protein Kinase ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Mitogen Activated Protein Kinase ◽  
Mrna Levels ◽  
Mitogen Activated Protein

Background/Aims: Poly r(C) binding protein (PCBP) 1 or heterogeneous ribonucleoprotein (hnRNP) E1 is a RNA binding protein functional in multiple biological processes. In prostate cancer (PCa), PCBP1 loss was shown to be involved with increased stemness in PCacells; however, the underlying mechanism remains unclear. Method: The role of PCBP1 in prostate tumor formationwas determined by xenograft assays. Immunoprecipitationand mass spectrometry were performed to find the pathways altered after PCBP1 knockdown. Cell proliferation, migration, invasion, and soft agar colony formationassays and xenograft assays were used to determine the role of target protein pathogenesis regulation and formation of PCa. QRT-PCR was performedto quantify relative mRNA expression. Results: The expression of mitogen activated protein kinase 1 (MAPK1) or extracellular signal regulated kinase 2 (ERK2) was increased following PCBP1 loss. Attenuation of MAPK1 inhibited in vitro and in vivo tumorigenicity and metastasis in PCa cell line, PC3. Overexpression of MAPK1 in the PC3 cells increased the tumorigenicity and metastasis. Analysis of PCBP1 and MAPK1 mRNA levels in 25 PCa patients compared to tumor-adjacent normal tissue confirmed an inverse correlation between PCBP1 and MAPK1 expression. Conclusions: PCBP1 can act as a suppressor of tumor in prostate epithelial cells by inhibiting MAPK1 expression.

scholarly journals Phosphorylation of the ARE-binding protein DAZAP1 by ERK2 induces its dissociation from DAZ

2006 ◽  
Vol 399 (2) ◽  
pp. 265-273 ◽  
Author(s):  
Simon Morton ◽  
Huei-Ting Yang ◽  
Ntsane Moleleki ◽  
David G. Campbell ◽  
Philip Cohen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Rna Binding ◽  
Binding Protein ◽  
Mitogen Activated Protein Kinase ◽  
Raw 264.7 ◽  
Raw 264.7 Macrophages ◽  
Hek 293 ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

A protein in RAW 264.7 macrophages, which became phosphorylated in response to LPS (lipopolysaccharide), was identified as the RNA-binding protein called DAZAP1 [DAZ (deleted in azoospermia)-associated protein 1]. The phosphorylation of this protein was prevented by specific inhibition of MKK1 [MAPK (mitogen-activated protein kinase) kinase 1], indicating that it was phosphorylated via the classical MAPK cascade. Further experiments showed that DAZAP1 was phosphorylated stoichiometrically in vitro by ERK2 (extracellular-signal-regulated protein kinase 2) at two Thr-Pro sequences (Thr269 and Thr315), and that both sites became phosphorylated in HEK-293 (human embryonic kidney 293) cells in response to PMA or EGF (epidermal growth factor), or RAW 264.7 macrophages in response to LPS. Phosphorylation induced by each stimulus was prevented by two structurally distinct inhibitors of MKK1 (PD184352 and U0126), demonstrating that DAZAP1 is a physiological substrate for ERK1/ERK2. The mutation of Thr269 and Thr315 to aspartate or the phosphorylation of these residues caused DAZAP1 to dissociate from its binding partner DAZ. DAZ interacts with PABP [poly(A)-binding protein] and thereby stimulates the translation of mRNAs containing short poly(A) tails [Collier, Gorgoni, Loveridge, Cooke and Gray (2005) EMBO J. 24, 2656–2666]. In the present study we have shown that DAZ cannot bind simultaneously to DAZAP1 and PABP, and suggest that the phosphorylation-induced dissociation of DAZ and DAZAP1 may allow the former to stimulate translation by interacting with PABP.

scholarly journals Role of the RNA-binding Protein Nrd1 and Pmk1 Mitogen-activated Protein Kinase in the Regulation of Myosin mRNA Stability in Fission Yeast

2009 ◽  
Vol 20 (9) ◽  
pp. 2473-2485 ◽  
Author(s):  
Ryosuke Satoh ◽  
Takahiro Morita ◽  
Hirofumi Takada ◽  
Ayako Kita ◽  
Shunji Ishiwata ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Fission Yeast ◽  
Mrna Stability ◽  
Rna Binding ◽  
Binding Protein ◽  
Myosin Ii ◽  
Rna Binding Protein ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein

Myosin II is an essential component of the actomyosin contractile ring and plays a crucial role in cytokinesis by generating the forces necessary for contraction of the actomyosin ring. Cdc4 is an essential myosin II light chain in fission yeast and is required for cytokinesis. In various eukaryotes, the phosphorylation of myosin is well documented as a primary means of activating myosin II, but little is known about the regulatory mechanisms of Cdc4. Here, we isolated Nrd1, an RNA-binding protein with RNA-recognition motifs, as a multicopy suppressor of cdc4 mutants. Notably, we demonstrated that Nrd1 binds and stabilizes Cdc4 mRNA, thereby suppressing the cytokinesis defects of the cdc4 mutants. Importantly, Pmk1 mitogen-activated protein kinase (MAPK) directly phosphorylates Nrd1, thereby negatively regulating the binding activity of Nrd1 to Cdc4 mRNA. Consistently, the inactivation of Pmk1 MAPK signaling, as well as Nrd1 overexpression, stabilized the Cdc4 mRNA level, thereby suppressing the cytokinesis defects associated with the cdc4 mutants. In addition, we demonstrated the cell cycle–dependent regulation of Pmk1/Nrd1 signaling. Together, our results indicate that Nrd1 plays a role in the regulation of Cdc4 mRNA stability; moreover, our study is the first to demonstrate the posttranscriptional regulation of myosin expression by MAPK signaling.

scholarly journals p38 Mitogen-activated protein kinase stabilizes SMN mRNA through RNA binding protein HuR

2009 ◽  
Vol 18 (21) ◽  
pp. 4035-4045 ◽  
Author(s):  
Faraz Farooq ◽  
Sylvia Balabanian ◽  
Xuejun Liu ◽  
Martin Holcik ◽  
Alex MacKenzie
Keyword(s):  
Protein Kinase ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein

INVESTIGATION OF THE ROLE OF GRSF-1 RNA BINDING PROTEIN IN PROSTATE CANCER PROGRESSION

1999 ◽  
pp. 61
Author(s):  
Michael E. Chen ◽  
Gail C. Fraizer ◽  
Tasneem Ahmed ◽  
Bei Zheng ◽  
Jeffrey Wilusz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Prostate Cancer Progression

scholarly journals Insulin acts via mitogen-activated protein kinase phosphorylation in rabbit blastocysts

Reproduction ◽  
2004 ◽  
Vol 128 (5) ◽  
pp. 517-526 ◽  
Author(s):  
Anne Navarrete Santos ◽  
Sarah Tonack ◽  
Michaela Kirstein ◽  
Marie Pantaleon ◽  
Peter Kaye ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Glucose Transport ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Preimplantation Embryos ◽  
Mrna Levels ◽  
Glut4 Translocation ◽  
Mitogen Activated Protein ◽  
Rabbit Embryos

The addition of insulin during in vitro culture has beneficial effects on rabbit preimplantation embryos leading to increased cell proliferation and reduced apoptosis. We have previously described the expression of the insulin receptor (IR) and the insulin-responsive glucose transporters (GLUT) 4 and 8 in rabbit preimplantation embryos. However, the effects of insulin on IR signaling and glucose metabolism have not been investigated in rabbit embryos. In the present study, the effects of 170 nM insulin on IR, GLUT4 and GLUT8 mRNA levels, Akt and Erk phosphorylation, GLUT4 translocation and methyl glucose transport were studied in cultured day 3 to day 6 rabbit embryos. Insulin stimulated phosphorylation of the mitogen-activated protein kinase (MAPK) Erk1/2 and levels of IR and GLUT4 mRNA, but not phosphorylation of the phosphatidylinositol 3-kinase-dependent protein kinase, Akt, GLUT8 mRNA levels, glucose uptake or GLUT4 translocation. Activation of the MAPK signaling pathway in the absence of GLUT4 translocation and of a glucose transport response suggest that in the rabbit preimplantation embryo insulin is acting as a growth factor rather than a component of glucose homeostatic control.

Role of mitogen-activated protein kinase pathway in acetylcholine-mediated in vitro relaxation of rat pulmonary artery

2002 ◽  
Vol 434 (1-2) ◽  
pp. 55-64 ◽  
Author(s):  
Wai Yee Choy ◽  
Yung Fat Wong ◽  
Yiu Wa Kwan ◽  
Alice Lai Shan Au ◽  
Wing Hung Lau ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Pulmonary Artery ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Kinase Pathway

scholarly journals Role of p38 mitogen-activated protein kinase in HIV type 1 production in vitro

1998 ◽  
Vol 95 (13) ◽  
pp. 7422-7426 ◽  
Author(s):  
L. Shapiro ◽  
K. A. Heidenreich ◽  
M. K. Meintzer ◽  
C. A. Dinarello
Keyword(s):  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Hiv Type 1

scholarly journals Post-transcriptional regulation of MEK-1 by polyamines through the RNA-binding protein HuR modulating intestinal epithelial apoptosis

2010 ◽  
Vol 426 (3) ◽  
pp. 293-306 ◽  
Author(s):  
Peng-Yuan Wang ◽  
Jaladanki N. Rao ◽  
Tongtong Zou ◽  
Lan Liu ◽  
Lan Xiao ◽  
...  
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Mitogen Activated Protein Kinase ◽  
Transcriptional Level ◽  
Intestinal Epithelial ◽  
Cellular Functions ◽  
Mitogen Activated Protein ◽  
Hu Antigen R ◽  
Post Transcriptional Regulation

MEK-1 [MAPK (mitogen-activated protein kinase) kinase-1] is an important signal transducing enzyme that is implicated in many aspects of cellular functions. In the present paper, we report that cellular polyamines regulate MEK-1 expression at the post-transcriptional level through the RNA-binding protein HuR (Hu-antigen R) in IECs (intestinal epithelial cells). Decreasing the levels of cellular polyamines by inhibiting ODC (ornithine decarboxylase) stabilized MEK-1 mRNA and promoted its translation through enhancement of the interaction between HuR and the 3′-untranslated region of MEK-1 mRNA, whereas increasing polyamine levels by ectopic ODC overexpression destabilized the MEK-1 transcript and repressed its translation by reducing the abundance of HuR–MEK-1 mRNA complex; neither intervention changed MEK-1 gene transcription via its promoter. HuR silencing rendered the MEK-1 mRNA unstable and inhibited its translation, thus preventing increases in MEK-1 mRNA and protein in polyamine-deficient cells. Conversely, HuR overexpression increased MEK-1 mRNA stability and promoted its translation. Inhibition of MEK-1 expression by MEK-1 silencing or HuR silencing prevented the increased resistance of polyamine-deficient cells to apoptosis. Moreover, HuR overexpression did not protect against apoptosis if MEK-1 expression was silenced. These results indicate that polyamines destabilize the MEK-1 mRNA and repress its translation by inhibiting the association between HuR and the MEK-1 transcript. Our findings indicate that MEK-1 is a key effector of the HuR-elicited anti-apoptotic programme in IECs.

Control of mRNA decay by phosphorylation of tristetraprolin

2008 ◽  
Vol 36 (3) ◽  
pp. 491-496 ◽  
Author(s):  
Heike Sandler ◽  
Georg Stoecklin
Keyword(s):  
Protein Kinase ◽  
Untranslated Region ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Mitogen Activated Protein Kinase ◽  
Interacting Proteins ◽  
Mitogen Activated Protein ◽  
Kinase Cascade ◽  
Transient Stabilization ◽  
Cytokine Mrnas

TTP (tristetraprolin) is an RNA-binding protein that suppresses inflammation by accelerating the degradation of cytokine mRNAs. TTP binds to an AU-rich element in the 3′-untranslated region of its target mRNAs. In macrophages, the induction of cytokine expression requires activation of the p38-MAPK (mitogen-activated protein kinase)–MK2 [MAPKAP (MAPK-activated protein) kinase-2] kinase cascade. MK2 directly phosphorylates TTP and thereby contributes to transient stabilization of cytokine mRNAs. In the present review, we address the target specificity of TTP, summarize TTP-interacting proteins and discuss how phosphorylation regulates the activity, localization and stability of TTP.

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