mVH1, a dual-specificity phosphatase whose expression is cell cycle regulated

Zhang, Xinmin; Dormady, Shane P.; Chaung, Wenren; Basch, Ross S.

doi:10.1007/s003350010198

Cited by 10 publications

(6 citation statements)

References 7 publications

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“…Further, L2dtl has a long 3Ј-untranslated region of 1878 bp. Many genes with long 3Ј-untranslated regions play a regulatory role during development (27). Indeed, human L2DTL protein is expressed in multiple fetal tissues, with very low levels in the adult tissues, a phenomenon similar to its Drosophila counterpart (1).…”

Section: Discussionmentioning

confidence: 99%

L2dtl Is Essential for Cell Survival and Nuclear Division in Early Mouse Embryonic Development

Liu

Pan

et al. 2007

Journal of Biological Chemistry

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l(2)dtl (lethal (2) denticleless), is an embryonic lethal homozygous mutation initially identified in Drosophila melanogaster that produces embryos that lack ventral denticle belts. In addition to nucleotide sequence, bioinformatic analysis has revealed a conservation of critical functional motifs among the human L2DTL, mouse L2dtl, and Drosophila l(2)dtl proteins. The function of the L2DTL protein in the development of mammalian embryos was studied using targeted disruption of the L2dtl gene in mice. The knock-out resulted in early embryonic lethality. L2dtl؊/؊ embryos were deformed and terminated development at the 4 -8-cell stage. Microinjection of a small interfering RNA (siRNA) vector (siRNA-L2dtl) into the two-cell stage nuclei of wild-type mouse embryos led to cell cycle progression failure, termination of cell division, and, eventually, embryonic death during the preimplantation stage. Morphological studies of the embryos 54 h after injection showed fragmentation of mitotic chromosomes and chromosomal lagging, hallmarks of mitotic catastrophe. The siRNA-L2dtl-treated embryos eventually lysed and failed to develop into blastocysts after 72 h of in vitro culturing. However, the embryos developed normally after they were microinjected into one nucleus of the two-celled embryos. The siRNA studies in HeLa cells showed that L2dtl protein depletion results in multinucleation and down-regulation of phosphatidylinositol 3-kinase, proliferating cell nuclear antigen, and PTTG1/securin, which might partially explain the mitotic catastrophe observed in L2dtl-depleted mouse embryos. Based on these findings, we conclude that L2dtl gene expression is essential for very early mouse embryonic development.

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Section: Discussionmentioning

confidence: 99%

L2dtl Is Essential for Cell Survival and Nuclear Division in Early Mouse Embryonic Development

Liu

Pan

et al. 2007

Journal of Biological Chemistry

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“…It is overexpressed in 10 of 10 tested samples and might be involved in the tumorigenesis of more aggressive ependymomas. This gene is located in a region often amplified in liposarcomas (43), and mRNA levels correlate with that of cyclin D1 throughout the cell cycle (44), suggesting a role in regulating cell division and potentially in neoplastic transformation.…”

Section: Discussionmentioning

confidence: 99%

Identification of Gains on 1q and Epidermal Growth Factor Receptor Overexpression as Independent Prognostic Markers in Intracranial Ependymoma

Meyer

Korshunov

Benner

et al. 2006

Clinical Cancer Research

209

191

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Purpose: Pathogenesis of ependymomas is still poorly understood and molecular markers for risk-adapted patient stratification are not available. Our aim was to screen for novel genomic imbalances and prognostic markers in ependymal tumors. Experimental Design: We analyzed 68 sporadic tumors by matrix-based comparative genomic hybridization using DNA microarrays containing >6,400 genomic DNA fragments. Novel recurrent genomic gains were validated by fluorescence in situ hybridization using a tissue microarray consisting of 170 intracranial ependymomas. Candidate genes were also tested for mRNA expression by quantitative real-time PCR, and protein expression was determined by immunohistochemistry on the tissue microarray. Results: Chromosomal gain of 1q correlated with pediatric patients (P = 0.004), intracranial ependymomas (P = 0.05), and tumors of grade III (P = 0.002). Gain of1q21.1-32.1was associated with tumor recurrence in intracranial ependymomas (P < 0.001). Furthermore, gain of 1q25 as determined by fluorescence in situ hybridization represented an independent prognostic marker for either recurrence-free survival (P < 0.001) or overall survival (P = 0.003). Recurrent gains at 5p15.33 covering hTERT were validated by immunohistochemistry, and elevated protein levels correlated with adverse prognosis (P = 0.01). In addition to frequent gains and high-level amplification of epidermal growth factor receptor (EGFR) at 7p11.2, immunohistochemistry revealed protein overexpression to be correlated with poor prognosis (P = 0.002). EGFR protein status subdivides intracranial grade II ependymomas into two different risk groups (P = 0.03) as shown by multivariate analysis. Conclusions: Thus, the states of 1q25 and EGFR represent independent prognostic markers for intracranial ependymomas to identify patient subgroups with different risk profiles in further clinical investigations. Moreover, EGFR might serve as therapeutic target for more specific chemotherapy applications.

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“…As mentioned above, there are eleven MKPs and many 'atypical' dual-specific phosphatases that dephosphorylate MAPK. However, none of these other phosphatases are known to be regulated during the cell cycle, except hYVH1 (DUSP12), 107 which is not known to act on MAPK and the CDC14 cell cycle phosphatases, which dephosphorylate cyclindependent kinases and other substrates during the exit from M phase. 108 Thus, cell cycle-dependent modulation of MAPK is currently on the shoulders of VHR alone.…”

Section: Vhr In Cell Cycle Regulationmentioning

confidence: 99%

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

Cerignoli¹,

Rahmouni²,

Ronai³

et al. 2006

Cell Cycle

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mVH1, a dual-specificity phosphatase whose expression is cell cycle regulated

Cited by 10 publications

References 7 publications

L2dtl Is Essential for Cell Survival and Nuclear Division in Early Mouse Embryonic Development

L2dtl Is Essential for Cell Survival and Nuclear Division in Early Mouse Embryonic Development

Identification of Gains on 1q and Epidermal Growth Factor Receptor Overexpression as Independent Prognostic Markers in Intracranial Ependymoma

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

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