SR Protein Kinase 1 Inhibition by TAF15
Although SRPKs were discovered nearly 30 years ago, our understanding of their mode of regulation is still limited. Regarded as constitutively active enzymes known to participate in diverse biological processes, their prominent mode of regulation mainly depends on their intracellular localization. M...
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MDPI AG
2022-12-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/1/126 |
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| author | Anastasia Koukiali Makrina Daniilidou Ilias Mylonis Thomas Giannakouros Eleni Nikolakaki |
| author_facet | Anastasia Koukiali Makrina Daniilidou Ilias Mylonis Thomas Giannakouros Eleni Nikolakaki |
| author_sort | Anastasia Koukiali |
| collection | DOAJ |
| description | Although SRPKs were discovered nearly 30 years ago, our understanding of their mode of regulation is still limited. Regarded as constitutively active enzymes known to participate in diverse biological processes, their prominent mode of regulation mainly depends on their intracellular localization. Molecular chaperones associate with a large internal spacer sequence that separates the bipartite kinase catalytic core and modulates the kinases’ partitioning between the cytoplasm and nucleus. Besides molecular chaperones that function as anchoring proteins, a few other proteins were shown to interact directly with SRPK1, the most-studied member of SRPKs, and alter its activity. In this study, we identified TAF15, which has been involved in transcription initiation, splicing, DNA repair, and RNA maturation, as a novel SRPK1-interacting protein. The C-terminal RGG domain of TAF15 was able to associate with SRPK1 and downregulate its activity. Furthermore, overexpression of this domain partially relocalized SRPK1 to the nucleus and resulted in hypophosphorylation of SR proteins, inhibition of splicing of a reporter minigene, and inhibition of Lamin B receptor phosphorylation. We further demonstrated that peptides comprising the RGG repeats of nucleolin, HNRPU, and HNRNPA2B1, were also able to inhibit SRPK1 activity, suggesting that negative regulation of SRPK1 activity might be a key biochemical property of RGG motif-containing proteins. |
| first_indexed | 2024-03-11T10:04:42Z |
| format | Article |
| id | doaj.art-2f66d967e6a74b3db10e8150b82b83a1 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T10:04:42Z |
| publishDate | 2022-12-01 |
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| series | Cells |
| spelling | doaj.art-2f66d967e6a74b3db10e8150b82b83a12023-11-16T15:06:26ZengMDPI AGCells2073-44092022-12-0112112610.3390/cells12010126SR Protein Kinase 1 Inhibition by TAF15Anastasia Koukiali0Makrina Daniilidou1Ilias Mylonis2Thomas Giannakouros3Eleni Nikolakaki4Laboratory of Biochemistry, Department of Chemistry, Aristotle University, 54124 Thessaloniki, GreeceLaboratory of Biochemistry, Department of Chemistry, Aristotle University, 54124 Thessaloniki, GreeceLaboratory of Biochemistry, Faculty of Medicine, University of Thessaly, Biopolis, 41500 Larissa, GreeceLaboratory of Biochemistry, Department of Chemistry, Aristotle University, 54124 Thessaloniki, GreeceLaboratory of Biochemistry, Department of Chemistry, Aristotle University, 54124 Thessaloniki, GreeceAlthough SRPKs were discovered nearly 30 years ago, our understanding of their mode of regulation is still limited. Regarded as constitutively active enzymes known to participate in diverse biological processes, their prominent mode of regulation mainly depends on their intracellular localization. Molecular chaperones associate with a large internal spacer sequence that separates the bipartite kinase catalytic core and modulates the kinases’ partitioning between the cytoplasm and nucleus. Besides molecular chaperones that function as anchoring proteins, a few other proteins were shown to interact directly with SRPK1, the most-studied member of SRPKs, and alter its activity. In this study, we identified TAF15, which has been involved in transcription initiation, splicing, DNA repair, and RNA maturation, as a novel SRPK1-interacting protein. The C-terminal RGG domain of TAF15 was able to associate with SRPK1 and downregulate its activity. Furthermore, overexpression of this domain partially relocalized SRPK1 to the nucleus and resulted in hypophosphorylation of SR proteins, inhibition of splicing of a reporter minigene, and inhibition of Lamin B receptor phosphorylation. We further demonstrated that peptides comprising the RGG repeats of nucleolin, HNRPU, and HNRNPA2B1, were also able to inhibit SRPK1 activity, suggesting that negative regulation of SRPK1 activity might be a key biochemical property of RGG motif-containing proteins.https://www.mdpi.com/2073-4409/12/1/126SRPK1TAF15RGG motifSR proteinsLBRnucleolin |
| spellingShingle | Anastasia Koukiali Makrina Daniilidou Ilias Mylonis Thomas Giannakouros Eleni Nikolakaki SR Protein Kinase 1 Inhibition by TAF15 Cells SRPK1 TAF15 RGG motif SR proteins LBR nucleolin |
| title | SR Protein Kinase 1 Inhibition by TAF15 |
| title_full | SR Protein Kinase 1 Inhibition by TAF15 |
| title_fullStr | SR Protein Kinase 1 Inhibition by TAF15 |
| title_full_unstemmed | SR Protein Kinase 1 Inhibition by TAF15 |
| title_short | SR Protein Kinase 1 Inhibition by TAF15 |
| title_sort | sr protein kinase 1 inhibition by taf15 |
| topic | SRPK1 TAF15 RGG motif SR proteins LBR nucleolin |
| url | https://www.mdpi.com/2073-4409/12/1/126 |
| work_keys_str_mv | AT anastasiakoukiali srproteinkinase1inhibitionbytaf15 AT makrinadaniilidou srproteinkinase1inhibitionbytaf15 AT iliasmylonis srproteinkinase1inhibitionbytaf15 AT thomasgiannakouros srproteinkinase1inhibitionbytaf15 AT eleninikolakaki srproteinkinase1inhibitionbytaf15 |