Vascular Biology and the Sex of Flies: Regulation of Vascular Smooth Muscle Cell Proliferation by Wilms’ Tumor 1–Associating Protein

Small, Theodore W.; Penalva, Luiz O. F.; Pickering, J. Geoffrey

doi:10.1016/j.tcm.2007.08.002

Cited by 20 publications

(17 citation statements)

References 36 publications

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“…3 WTAP is a highly conserved protein that partners with WT1 4,5 to function as a switch gene, regulating the balance between quiescence and proliferation. 6 WTAP-null mice exhibit embryonic lethality. 7 WTAP has been recently described as an oncogenic factor in gliomas.…”

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confidence: 99%

WTAP is a novel oncogenic protein in acute myeloid leukemia

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Yihua

Iyer³

et al. 2014

Leukemia

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confidence: 99%

WTAP is a novel oncogenic protein in acute myeloid leukemia

Bansal

Yihua

Iyer³

et al. 2014

Leukemia

221

232

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“…×400 in A3-E3 WTAP was found over-expressed in breast carcinoma and acute leukemia. Du-Il Jin found that WTAP expression was greater in GBM than in normal brain tissues and WTAP could regulate proliferation, migration, and invasion of GBM cell lines (Jin et al 2012;Small et al 2007). They performed IHC assay using 10 GBM patients' tissues only for detecting the expression of WTAP and confirmed that WTAP-positive cells are glioblastoma cells.…”

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confidence: 99%

WTAP Expression Predicts Poor Prognosis in Malignant Glioma Patients

Xue

Zheng

et al. 2016

J Mol Neurosci

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Wilms' tumor 1-associating protein (WTAP) interacts with the Wilms' tumor 1 gene. Although originally classified as a tumor suppressor, WTAP was later found to be over-expressed in glioblastoma which is regarded as a grade IV astrocytoma. However, the expression in other glioma grades and the relationship between WTAP expression and the prognosis of glioma patients are still unknown. In this study, we investigated WTAP expression in 169 different types of glioma cases using western blot analysis and immunohistochemistry assay. Further, we evaluated the association of WTAP expression with clinicopathological characteristics using chi-square test and Spearman's correlation test. We used univariate and multivariate Cox regression analyses to evaluate the independency of diferent WTAP expression. Then, the survival curves were calculated using the Kaplan-Meier method. Results showed that WTAP was over-expressed in glioma tissues, and the expression was closely correlated with glioma grade. Moreover, high WTAP expression was correlated with poor postoperative survival in glioma patients. WTAP may serve as a novel prognostic marker.

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“…Another level of action relates to the ability of WTAP to prevent WT1 from binding to its transcriptional target DNA (4). There is also evidence that WTAP may act as a splicing regulator (7). In this regard, it is noteworthy that WTAP is the mammalian homolog of Drosophila Fl(2)d (female-lethal-2-d), a protein that is necessary for regulating alternative splicing of several pre-mRNA species.…”

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confidence: 99%

Nuclear Degradation of Wilms Tumor 1-associating Protein and Survivin Splice Variant Switching Underlie IGF-1-mediated Survival

Small

Pickering

2009

Journal of Biological Chemistry

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WTAP (Wilms tumor 1-associating protein) is a recently identified nuclear protein that is essential for mouse embryo development. The Drosophila homolog of WTAP, Fl(2)d, regulates pre-mRNA splicing; however, the role of WTAP in mammalian cells is uncertain. To elucidate a context for WTAP action, we screened growth and survival factors for their effects on WTAP expression in vascular smooth muscle cells (SMCs), a cell type previously found to express WTAP dynamically. This revealed that insulin-like growth factor-1 (IGF-1) uniquely reduced WTAP abundance. This decline in WTAP proved to be necessary for IGF-1 to confer its antiapoptotic properties, which were blocked by transducing the WTAP gene into SMCs. WTAP down-regulation by IGF-1 was mediated by an IGF-1 receptorphosphatidylinositol 3-kinase-Akt signaling axis that directed WTAP degradation via a nuclear 26 S proteasome. Moreover, by promoting the degradation of WTAP, IGF-1 shifted the pre-mRNA splicing program for the survival factor, survivin, to reduce expression of survivin-2B, which is proapoptotic, and increase expression of survivin, which is antiapoptotic. Knockdown of survivin-2B rescued the ability of IGF-1 to promote survival when WTAP was overexpressed. These data uncover a novel regulatory cascade for human SMC survival based on adjusting the nuclear abundance of WTAP to define the splice variant balance among survivin isoforms. Smooth muscle cell (SMC)3 survival is critical to vascular stability (1). This is especially important during atherosclerosis, a condition that depends on replicating SMCs to mechanically stabilize the artery wall. An abundance of proapoptotic stimuli within an atherosclerotic lesion can deplete the SMC population, resulting in plaque rupture and myocardial infarction (1, 2). Pathways that enable SMCs to replicate and perform reparative functions and simultaneously resist apoptotic signals are therefore vital to cardiovascular health.WTAP (Wilms tumor 1-associating protein) is a recently identified nuclear protein that, as its name implies, can interact with the WT1 suppressor protein (3, 4). The precise molecular actions of WTAP are not well understood, but the importance of this protein is highlighted by the early lethality of WTAP-null mouse embryos (5, 6). WTAP is widely expressed in adult tissues and might therefore play a constitutive role. However, expression of WTAP can also be dynamic. We found that WTAP expression in the adult artery wall varied, depending on whether the vessel was quiescent or remodeling. In particular, WTAP abundance decreased as vascular SMCs were induced to proliferate and increased as remodeling subsided and SMC accumulation terminated. Furthermore, overexpression of WTAP in cultured SMCs suppressed their accumulation, whereas WTAP knockdown stimulated population growth. These effects were mediated, at least in part, by the capacity for WTAP to activate apoptosis (4).The basis by which WTAP impacts cell function is uncertain, and several possibilities have been raised. One group has repor...

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Vascular Biology and the Sex of Flies: Regulation of Vascular Smooth Muscle Cell Proliferation by Wilms’ Tumor 1–Associating Protein

Cited by 20 publications

References 36 publications

WTAP is a novel oncogenic protein in acute myeloid leukemia

WTAP is a novel oncogenic protein in acute myeloid leukemia

WTAP Expression Predicts Poor Prognosis in Malignant Glioma Patients

Nuclear Degradation of Wilms Tumor 1-associating Protein and Survivin Splice Variant Switching Underlie IGF-1-mediated Survival

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