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Serine/arginine protein-specific kinase 2 promotes leukemia cell proliferation by phosphorylating acinus and regulating cyclin A1

Jang, Sung-Wuk; Yang, Seung-ju; Ehlén, Åsa LU ; Dong, Shaozhong; Khoury, Hanna; Chen, Jing; Persson, Jenny L LU and Ye, Keqiang (2008) In Cancer Research 68(12). p.4559-4570
Abstract
Serine/arginine (SR) protein-specific kinase (SRPK), a family of cell cycle-regulated protein kinases, phosphorylate SR domain-containing proteins in nuclear speckles and mediate the pre-mRNA splicing. However, the physiologic roles of this event in cell cycle are incompletely understood. Here, we show that SRPK2 binds and phosphorylates acinus, an SR protein essential for RNA splicing, and redistributes it from the nuclear speckles to the nucleoplasm, resulting in cyclin A1 but not A2 up-regulation. Acinus S422D, an SRPK2 phosphorylation mimetic, enhances cyclin A1 transcription, whereas acinus S422A, an unphosphorylatable mutant, blocks the stimulatory effect of SRPK2. Ablation of acinus or SRPK2 abrogates cyclin A1 expression in... (More)
Serine/arginine (SR) protein-specific kinase (SRPK), a family of cell cycle-regulated protein kinases, phosphorylate SR domain-containing proteins in nuclear speckles and mediate the pre-mRNA splicing. However, the physiologic roles of this event in cell cycle are incompletely understood. Here, we show that SRPK2 binds and phosphorylates acinus, an SR protein essential for RNA splicing, and redistributes it from the nuclear speckles to the nucleoplasm, resulting in cyclin A1 but not A2 up-regulation. Acinus S422D, an SRPK2 phosphorylation mimetic, enhances cyclin A1 transcription, whereas acinus S422A, an unphosphorylatable mutant, blocks the stimulatory effect of SRPK2. Ablation of acinus or SRPK2 abrogates cyclin A1 expression in leukemia cells and arrest cells at G, phase. Overexpression of acinus or SRPK2 increases leukemia cell proliferation. Furthermore, both SRPK2 and acinus are overexpressed in some human acute myelogenous leukemia patients and correlate with elevated cyclin A1 expression levels, fitting with the oncogenic activity of cyclin A1 in leukemia. Thus, our findings establish a molecular mechanism by which SR splicing machinery regulates cell cycle and contributes to leukemia tumorigenesis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Research
volume
68
issue
12
pages
4559 - 4570
publisher
American Association for Cancer Research Inc.
external identifiers
  • wos:000256855700012
  • scopus:49649101933
ISSN
1538-7445
DOI
10.1158/0008-5472.CAN-08-0021
language
English
LU publication?
yes
id
231e04fc-6bdc-4d0f-8947-ca287fc7c9c9 (old id 1191144)
date added to LUP
2008-09-08 11:45:27
date last changed
2017-10-22 04:24:32
@article{231e04fc-6bdc-4d0f-8947-ca287fc7c9c9,
  abstract     = {Serine/arginine (SR) protein-specific kinase (SRPK), a family of cell cycle-regulated protein kinases, phosphorylate SR domain-containing proteins in nuclear speckles and mediate the pre-mRNA splicing. However, the physiologic roles of this event in cell cycle are incompletely understood. Here, we show that SRPK2 binds and phosphorylates acinus, an SR protein essential for RNA splicing, and redistributes it from the nuclear speckles to the nucleoplasm, resulting in cyclin A1 but not A2 up-regulation. Acinus S422D, an SRPK2 phosphorylation mimetic, enhances cyclin A1 transcription, whereas acinus S422A, an unphosphorylatable mutant, blocks the stimulatory effect of SRPK2. Ablation of acinus or SRPK2 abrogates cyclin A1 expression in leukemia cells and arrest cells at G, phase. Overexpression of acinus or SRPK2 increases leukemia cell proliferation. Furthermore, both SRPK2 and acinus are overexpressed in some human acute myelogenous leukemia patients and correlate with elevated cyclin A1 expression levels, fitting with the oncogenic activity of cyclin A1 in leukemia. Thus, our findings establish a molecular mechanism by which SR splicing machinery regulates cell cycle and contributes to leukemia tumorigenesis.},
  author       = {Jang, Sung-Wuk and Yang, Seung-ju and Ehlén, Åsa and Dong, Shaozhong and Khoury, Hanna and Chen, Jing and Persson, Jenny L and Ye, Keqiang},
  issn         = {1538-7445},
  language     = {eng},
  number       = {12},
  pages        = {4559--4570},
  publisher    = {American Association for Cancer Research Inc.},
  series       = {Cancer Research},
  title        = {Serine/arginine protein-specific kinase 2 promotes leukemia cell proliferation by phosphorylating acinus and regulating cyclin A1},
  url          = {http://dx.doi.org/10.1158/0008-5472.CAN-08-0021},
  volume       = {68},
  year         = {2008},
}