Protein kinases that phosphorylate splicing factors: Roles in cancer development, progression and possible therapeutic options

Czubaty, Alicja; Piekiełko-Witkowska, Agnieszka

doi:10.1016/j.biocel.2017.05.024

Cited by 47 publications

(44 citation statements)

References 130 publications

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“…SRPK1 and SRPK2 are cellular kinases that shuttle between the cytosol and nucleus and target proteins containing serine–arginine-rich domains (SR proteins, for a review, see Czubaty et al . (33)). It has been reported that SRPK1 also phosphorylates viral proteins (34-38).…”

Section: Discussionmentioning

confidence: 99%

Serine-arginine protein kinase 1 regulates Ebola virus transcription

Takamatsu

Krähling

Kolesnikova

et al. 2019

Preprint

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word count: 148) 13Ebola virus (EBOV) causes a severe and often fatal disease for which no approved 14 vaccines or antivirals are currently available. EBOV transcription requires the sequential 15 phosphorylation and dephosphorylation of the viral transcription factor VP30. While 16 dephosphorylation is carried out by phosphatases PP2A and PP1, the VP30-specific 17 kinase is unknown. Here, we report that serine-arginine protein kinase 1 and 2 (SRPK1 18 and SRPK2) phosphorylate serine-29 of VP30, which is located in an N-terminal R26xxS29 19 motif. Interaction with VP30 via the R26xxS29 motif recruits SRPK1 into EBOV-induced 20 inclusion bodies, the sites of viral RNA synthesis and an inhibitor of SRPK1/SRPK2 21 downregulates primary viral transcription. When the SRPK1 recognition motif of VP30 22 was mutated in a recombinant EBOV, virus replication was severely impaired. It is 23 presumed that the interplay between SRPK1 and PP2A in the EBOV inclusions provides 24 a comprehensive regulatory circuit to ensure the activity of VP30 in EBOV transcription. 25 26 inhibit ectopically expressed SRPK1 ( Figure 2B, lanes 2 and 4). Quantification of three 130 independent experiments confirmed the statistical significance of the observations 131 ( Figure 2B, graph). In summary, SRPK1 specifically phosphorylates VP30 wt and VP30 29S 132 in vitro and in cultured cells and regulates the phosphorylation state of VP30 together 133 with OA-sensitive phosphatases, likely PP2A and/or PP1. 134 SRPK1 regulates EBOV genome transcription/replication

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Section: Discussionmentioning

confidence: 99%

Serine-arginine protein kinase 1 regulates Ebola virus transcription

Takamatsu

Krähling

Kolesnikova

et al. 2019

Preprint

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“…The development and progression of malignant tumors constitutes a complex process that is affected by numerous factors, including the biological characteristics of the tumor cells themselves (31,32). The poor prognosis of breast cancer, which is one of the most common and lethal malignant diseases, is due to its metastasis (33,34).…”

Section: Discussionmentioning

confidence: 99%

SKA2 mediates invasion and metastasis in human breast cancer via EMT

Ren

Yang

Zhang³

et al. 2018

Mol Med Report

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Spindle and kinetochore-associated protein 2 (SKA2) is essential for regulating the progression of mitosis. In recent years, SKA2 upregulation has been detected in various human malignancies and the role of SKA2 in tumorigenesis has received increasing attention. However, the expression and functional significance of SKA2 in breast cancer are not completely understood. To study the effects of SKA2 on breast cancer, the expression levels of SKA2 in breast cancer tissues and cell lines were evaluated by western blotting, reverse transcription-quantitative polymerase chain reaction and immunohistochemical staining. The results demonstrated that SKA2 expression was increased in breast cancer tissues and cells, and SKA2 overexpression was associated with clinical stage and lymph node metastasis. Functional investigations revealed that SKA2 knockdown in breast cancer cells significantly reduced migration and invasion, and resulted in the decreased expression levels of matrix metalloproteinase (MMP)2 and MMP9. Furthermore, the typical microtubule arrangement was altered in SKA2 small interfering RNA (siSKA2)-transfected cells. Reduced levels of SKA2 also downregulated the expression of epithelial-mesenchymal transition proteins, including fibronectin, N-cadherin and vimentin, whereas there were no alterations in the protein expression levels of E-cadherin. Conversely, upregulation of SKA2 decreased the expression levels of E-cadherin, and increased N-cadherin, fibronectin and vimentin levels. Notably, it was demonstrated that E-cadherin was translocated from the cytoplasm to the nucleus in siSKA2-transfected cells.These results demonstrated that SKA2 may be associated with breast cancer metastasis, and siSKA2 inhibited the invasion and metastasis of breast cancer via translocation of E-cadherin from the cytoplasm to the nucleus. SKA2 mediates invasion and metastasis in human breast cancer via EMT

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“…Any dysregulation of apoptosis can result in abnormality, disease and death. Cancer is a result of uncontrolled cell proliferation and apoptosis dysregulation [24]. Therefore, the induction of apoptosis is a highly desirable mechanism for cancer treatment [25].…”

Section: Discussionmentioning

confidence: 99%

The Mechanistic Antitumor Study of Myricanol 5-Fluorobenzyloxy Ether in Human Leukemic Cell Hl-60

Dai

Fan

Ren³

et al. 2017

Future Med. Chem.

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Aim:The aim of the study was to explore the growth inhibitory effect of myricanol 5-fluorobenzyloxy ether (5FEM) and the underlying mechanism in human leukemic cells HL-60. Materials & methods: 5FEM was obtained by chemical modification of myricanol with fluorobenzyloxy ether at the OH(5) position. The cytotoxicity, cell apoptosis, cell cycle and the expression of key apoptosis-related genes in HL-60 were evaluated. Results & conclusion: 5FEM can significantly inhibited growth of HL-60 cells, increased the G2/M population and upregulated the expression of Bax, Fas, FasL, caspase-9 and p21 and downregulated that of Bcl-2 and survivin. The results enhance our understanding of 5FEM and aid the discovery of novel myricanol derivatives as potential antitumor agents. The incidence and mortality of cancer have been increasing in China [1]. About 4,292,000 new cases of cancer and 2,814,000 cancer-related deaths were estimated in China in 2015 [2]. It was reported that leukemia is the sixth leading cause of cancer death [3].Both genetic and environmental factors have been reported to cause of leukemia [4,5]. Combination of chemotherapy, radiation therapy and bone marrow transplant are involved in treatment of leukemia [6]. But these treatments have limitations because of a high probability of relapse and toxicity. Traditional Chinese medicine and natural plants have been used in the treatment of cancer for thousands of years in China. Owing to its minor side effects and good curative efficacy, the screening of anticancer drugs from traditional Chinese herbal medicine has increased considerably over the past few years [7,8].Myrica rubra (Lour.) Sieb. Et Zucc., a myricaceae Myrica plant, found in China and other Asian countries. Because of its biological properties, the bark of M. rubra is used in Chinese folk medicine [9][10][11]. Myricanol is a cyclic diarylheptanoid isolated from the bark of M. rubra. Diarylheptanoids exhibit various biological activities, including antitumor [12], antiviral [13], antioxidant [14] and anti-inflammatory [15] owing to its unique chemical structure. Our previous studies have shown that myricanol significantly inhibits the proliferation of human lung adenocarcinoma (A549), hepatoma (HepG2) and human promyelocytic leukemia (HL-60) cells. Further, it increased the caspase-3, caspase-9, Bax and p21 expression and decreased the expressions of Bcl-2 at the mRNA and protein levels [16]. Myricanol significantly induced tumor growth inhibitory effects on the xenografts of lung adenocarcinoma A549 by upregulating the expression of Bax and downregulating that of survivin, Bcl-2, VEGF and HIF-1α. The experimentation has indicated that the possible antitumor effects of myricanol are via the mitochondrial apoptosis pathway [17].In order to improve anticancer effect of myricanol, and to further explore the structure-activity relationship of myricanol and discover novel myricanol derivatives as antitumor agents, some novel myricanol derivatives, such as 5-fluorobenzyloxy ether (5FEM), myricanol 5-chlorobe...

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Protein kinases that phosphorylate splicing factors: Roles in cancer development, progression and possible therapeutic options

Cited by 47 publications

References 130 publications

Serine-arginine protein kinase 1 regulates Ebola virus transcription

Serine-arginine protein kinase 1 regulates Ebola virus transcription

SKA2 mediates invasion and metastasis in human breast cancer via EMT

The Mechanistic Antitumor Study of Myricanol 5-Fluorobenzyloxy Ether in Human Leukemic Cell Hl-60

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