Regulation of MAP Kinases by the VHR Dual-Specific Phosphatase – Implications for Cell Growth and Differentiation

Cerignoli, Fabio; Rahmouni, Souad; Ronai, Ze’ev; Mustelin, Tomas

doi:10.4161/cc.5.19.3267

Cited by 36 publications

(40 citation statements)

References 118 publications

(101 reference statements)

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“…100 This supports findings by Yan et al in mature murine and human colonic epithelia. They demonstrated that LGG prevented cytokineinduced apoptosis by activating anti-apoptotic genes (Akt/protein kinase B) and inhibiting activation of pro-apoptotic genes (p38/ MAP-kinase).…”

Section: Discussionsupporting

confidence: 90%

Developmental biology of gut-probiotic interaction

Patel

Lin

2010

Gut Microbes

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Section: Discussionsupporting

confidence: 90%

Developmental biology of gut-probiotic interaction

Patel

Lin

2010

Gut Microbes

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“…Gradually, it accumulates by means of its augmented transcription during late G1 and S phases. 5 The siRNA interference analyses also show that depletion of VHR phosphatase arrests cells at the G 1 /S, and G 2 /M phases. 5 Highly active extracellular signal regulated kinase (ERK) is a main reason of the cell cycle arrest.…”

mentioning

confidence: 99%

“…5 The siRNA interference analyses also show that depletion of VHR phosphatase arrests cells at the G 1 /S, and G 2 /M phases. 5 Highly active extracellular signal regulated kinase (ERK) is a main reason of the cell cycle arrest. 6 Elevated VHR phosphatase expression results in cell cycle progression by dephosphorylating ERK.…”

mentioning

confidence: 99%

Regulation of Vaccinia H1-related (VHR) Phosphatase Activity by NSC-87877

Park¹,

Song²,

Cho

2009

Bulletin of the Korean Chemical Society

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Half maximal inhibitory constant of enzyme was determined to 7.83 ± 0.98 µM. VHR phosphatase (100 nM) was incubated with various concentrations of NSC-87877 at 37 o C for 30 min. Fluorescence emission from the product was measured with a multiwell plate reader as described in Experimental section.Based on amino-acid sequences of catalytic domains, protein tyrosine phosphatases (PTPs) can be classified into four groups 1 ; class I Cys-based PTPs, class II Cys-based PTPs, class III Cys-based PTPs, and Asp-based PTPs. Each PTP has a characteristic role in a variety of cellular processes including cellular metabolism, growth, proliferation, differentiation and also has been emerged as a therapeutic target in many diseases such as diabetes, leukemia, neurodegradation, and cancer. Class I PTPs comprise dual specificity phosphatases (DUSPs) including VHR that has diverse substrate specificities both or either on phospho-Tyr, phospho-Ser, and phospho-Thr residues. Class II PTPs that dephosphorylate only pTyr are encoded by a single gene ACP1 and related to diseases like Alzheimer's disease and asthma. Class III PTPs comprise CDC25 family proteins that regulate cell cycle by acting on Cdks. They dephosphorylate Thr-Tyr motifs of N-terminal Cdks, thus keep them from driving the cell progression.2 Asp-based PTPs encoded by only four Eya genes recently have been listed as a new family.VHR phosphatase, also called DUSP3, is a 20 kDa protein that might be one of the smallest known PTPs. VHR phosphatase can be elucidated by two particular characteristics in cellular physiology. First, VHR phosphatase shows more expression in the nucleus of cancer cells than that of normal cells. It is not due to the increase of transcription of VHR gene, but due to stabilization VHR phosphatase in cancer cell. Its expression was increased in cervix carcinoma and prostate cancer. 4 Another intriguing aspect of VHR phosphatase is that it fluctuates during the phases of cell cycle. VHR phosphatase during G1 phase is not detected due to rapid degradation. Gradually, it accumulates by means of its augmented transcription during late G1 and S phases. 5 The siRNA interference analyses also show that depletion of VHR phosphatase arrests cells at the G 1 /S, and G 2 /M phases. 5 Highly active extracellular signal regulated kinase (ERK) is a main reason of the cell cycle arrest. 6 Elevated VHR phosphatase expression results in cell cycle progression by dephosphorylating ERK. Due to its elevated protein level in cancers such as cervix carcinoma and prostate cancer and involvement in cell cycle progression, VHR phosphatase has been emerged as a therapeutic target. Therefore, it is important to identify novel inhibitor of VHR phosphatase for cancer treatment. Several VHR phosphatase inhibitors including stevastelins, 7 glucosamine-aminoehoxy triphenyltin (GATPT), 8 RK-682, 9 and 4-iA 10 have been identified so far. In search for more putative VHR phosphatase inhibitors, we investigated whether 8-hydroxy-7-[(6-sulfo-2-naphthyl)azo]-5-quinolinesulfonic acid ...

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“…Supporting this possibility, we show that addition of MEIS1 CTD to full-length PKNOX1 is sufficient for activation of Meis1-associated oncogenic pathways and that MEIS1 and PKNOX1 differentially regulate the expression of a subset of genes involved in cellular proliferation, such as Vhr (Dusp3). 46 Together, results presented in this report show that elevated levels of MEIS1 perturb expression of numerous genes implicated in several oncogenic pathways, and suggest a direct role for PKNOX1 in attenuation of the pro-tumorigenic activity of MEIS1. …”

mentioning

confidence: 76%

C-terminal domain of MEIS1 converts PKNOX1 (PREP1) into a HOXA9-collaborating oncoprotein

Bisaillon

Wilhelm

Krošl

et al. 2011

Blood

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The three-amino-acid loop extension (TALE) class homeodomain proteins MEIS1 and PKNOX1 (PREP1) share the ability to interact with PBX and HOX family members and bind similar DNA sequences but appear to play opposing roles in tumor development. Elevated levels of MEIS1 accelerate development of HOX-and MLL-induced leukemias, and this pro-tumorigenic property has been associated with transcriptional activity of MEIS1. In contrast, reduction of PKNOX1 levels has been linked with cancer development despite the absence of an identifiable transactivating domain. In this report, we show that a chimeric protein generated by fusion of the MEIS1 C-terminal region encompassing the transactivating domain with the full-length PKNOX1 (PKNOX1- MC IntroductionThere is a compelling body of evidence implicating the HOX transcription factors and their cofactors PBX and MEIS/PKNOX-(PREP) in leukemogenesis (reviewed by Argiropoulos et al 1 ). In particular, deregulated expression of HOXA9 has been detected in a large proportion of human acute myeloid (AML) and lymphoid leukemias (ALLs) [2][3][4][5] and is associated with poor prognosis for refractory AML. 2 A significant proportion of these leukemias, especially those harboring MLL rearrangements, also overexpress MEIS1, [3][4][5][6] indicating that activation of MEIS1 may represent a key collaborating genetic event in leukemia development.MEIS1 is a member of the TALE class of homeoproteins, which includes the PBX and MEIS/PKNOX protein families characterized by an atypical homeodomain (HD) containing a three-amino acid loop extension (TALE) between the first 2 ␣-helices. 7 MEIS1/PKNOX1 and PBX1 proteins physically interact with each other using the bipartite Homothorax-MEIS domain (HM A /HM B ) and the PBC-A domain of PBX. 8,9 This interaction was reported to enhance the stability of the heterodimers and to promote their nuclear localization. [10][11][12] MEIS1 and PBX1 also form heterodimers with HOX proteins in a DNAdependent manner and have been reported to form triple complexes composed of MEIS1/PKNOX1, PBX1, and HOX in both a DNA-independent 13,14 and DNA-dependent manner, 15 suggesting that, in some cellular contexts, a triple HOX-PBX-MEIS/PKNOX complex is required for HOX-mediated gene regulation. 15,16 The combinatorial diversity generated by 39 different Hox, 3 Meis, 2 Pknox, and 4 Pbx gene products probably enables formation of distinct regulatory complexes targeting numerous genomic loci in a cell context-dependent manner.Using a bone marrow transduction/transplantation-based experimental model, we showed that overexpression of Meis1 significantly accelerates the onset of Hoxa9-induced AML, 17,18 and similar collaborative Meis1 effects were reported for other Hox and Hox-fusion genes tested. 19,20 High levels of Meis1 expression also appeared to be the rate-limiting factor for development of Mllinduced leukemias, 21 implying that Meis1 activity is necessary to create and/or maintain cellular context required for tumor development. Pknox1 overexpression, in contrast, fai...

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Regulation of MAP Kinases by the VHR Dual-Specific Phosphatase – Implications for Cell Growth and Differentiation

Cited by 36 publications

References 118 publications

Developmental biology of gut-probiotic interaction

Developmental biology of gut-probiotic interaction

Regulation of Vaccinia H1-related (VHR) Phosphatase Activity by NSC-87877

C-terminal domain of MEIS1 converts PKNOX1 (PREP1) into a HOXA9-collaborating oncoprotein

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