Cited by 124RNA Research and SplicingCancer-related Molecular PathwaysSignaling Pathways in Disease

Characterization of Cyclin L2, a Novel Cyclin with an Arginine/Serine-rich Domain

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de Graaf, Katrin, Hekerman, Paul, Spelten, Oliver, Herrmann, Andreas, Packman, Len C., Büssow, Konrad, Müller-Newen, Gerhard, Becker, Walter·2004·Journal of Biological Chemistry

Abstract

A novel method employing filter arrays of a cDNA expression library for the identification of substrates for protein kinases was developed. With this technique, we identified a new member of the cyclin family, cyclin L2, as a substrate of the nuclear protein kinase DYRK1A. Cyclin L2 contains an N-terminal cyclin domain and a C-terminal arginine/serine-rich domain (RS domain), which is a hallmark of many proteins involved in pre-mRNA processing. The gene for cyclin L2 encodes the full-length cyclin L2, which is predominantly expressed in testis, as well as a truncated splicing variant (cyclin L2S) that lacks the RS domain and is ubiquitously expressed in human tissues. Full-length cyclin L2, but not cyclin L2S, was associated with the cyclin-dependent kinase PITSLRE. Cyclin L2 interacted with splicing factor 2 in vitro and was co-localized with the splicing factor SC35 in the nuclear speckle compartment. Photobleaching experiments showed that a fusion protein of green fluorescent protein and cyclin L2 in nuclear speckles rapidly exchanged with unbleached molecules in the nucleus, similar to other RS domain-containing proteins. In striking contrast, the closely related green fluorescent protein-cyclin L1 was immobile in the speckle compartment. DYRK1A interacted with cyclin L2 in pull-down assays, and overexpression of DYRK1A stimulated phosphorylation of cyclin L2 in COS-7 cells. These data characterize cyclin L2 as a highly mobile component of nuclear speckles and suggest that DYRK1A may regulate splicing by phosphorylation of cyclin L2.

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  • The substrates regulated by DYRK1A phosphorylation are located in both the nucleus and cytosol, and this regulation is likely to be tissue- and time-specific.

    “The substrates regulated by DYRK1A phosphorylation are located in both the nucleus and cytosol, and this regulation is likely to be tissue and time-specific (Arron et al., 2006; Chen-Hwang et al., 2002; de Graaf et al., 2004; Kaczmarski et al., 2014; Marti et al., 2003; Woods et al., 2001).”

    From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as de Graaf et al., 2004

    The introductory passage (labeled Abstract in our copy; page unavailable) identifies nuclear transcription factors as DYRK1A substrates and says cytoplasmic proteins have been reported to be phosphorylated by DYRK1A, while cautioning that those proteins might instead be targets of DYRK2 or DYRK3. The Discussion identifies additional nuclear substrates. Neither passage supports the claim that DYRK1A phosphorylation is likely to be tissue- and time-specific. (LLM, conf=0.86)

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Research works printed but not linked: 4

  1. Ha ¨mmerle, B., Elizalde, C., Galceran, J., Becker, W., and Tejedor, F. J. (2003) J. Neural Transm. Suppl., in press
  2. Galceran, J., de Graaf, K., Tejedor, F. J., and Becker, W. (2003) J. Neural Transm. Suppl., in press
  3. Brinkworth, R. I., Breinl, R. A., and Kobe, B. (2003) Proc. Natl. Acad. Sci.
  4. Mortillaro, M. J., Blencowe, B. J., Wei, X., Nakayasu, H., Du, L., Warren, S. L., Sharp, P. A., and Berezney, R. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 8253-8257

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Authors
de Graaf, K., Hekerman, P., Spelten, O., Herrmann, A., Packman, L. C., Büssow, K., Müller-Newen, G., & Becker, W.
Affiliations
  • RWTH Aachen University (DE)
  • University of Cambridge (GB)
  • Max Planck Institute for Molecular Genetics (DE)
Corresponding author
Becker, Walter
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2004-02
Volume
279
Issue
6
Pages
4612-4624
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2118731883
Cited by
124
References
66
Citations by year
2025: 1 · 2024: 1 · 2023: 5 · 2022: 1 · 2021: 14 · 2020: 2 · 2019: 6 · 2018: 3 · 2017: 1 · 2016: 4 · 2015: 4 · 2014: 1 · 2013: 3 · 2012: 10
FWCI
4.15
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
Funders
Deutsche Forschungsgemeinschaft (SFB 542)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords
arginine/serine-rich domain, DYRK1A, filter arrays, pre-mRNA splicing, nuclear speckles, SRSF2, cyclin-dependent kinases, protein phosphorylation, testis-specific gene expression
MeSH terms
Dyrk Kinases, Amino Acid Sequence, Animals, Arginine, Base Sequence, Cell Nucleus, Humans, Male, Molecular Sequence Data, Phosphorylation, Protein-Tyrosine Kinases, Recombinant Fusion Proteins, RNA Splicing, Serine, Substrate Specificity, Transcription Factors, Cyclins, Protein Serine-Threonine Kinases, Protein Structure, Tertiary, DNA, Complementary, COS Cells, Mice, Rats, In Vitro Techniques

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