Scorpins in the DNA Damage Response
<p>Schematic representation of RANBP9 and RANBP10 proteins. RANBP10 shares high amino acid conservation with RANBP9 in the PRY (94%), SPRY (97%), LisH (82%), CTLH (90%), and CRA (89%) domains. The two proteins differ the most at the N-terminus and in the post-CTLH region, which contains several putative PIK-kinase phosphorylation sites (see <a href="#ijms-19-01794-t001" class="html-table">Table 1</a>). PRD (red)= Proline-Rich Domain; PRY/SPRY (light blue) = Spore lysis A and Ryanodine receptor Domain; LisH (green) = Lissencephaly type-I-like homology motif; CTLH (yellow) = Carboxy-terminal to LisH motif domain; CRA (orange) = CT11-RanBP9 domain; dark blue = putative Nuclear Localization Signal; Tub (purple) = tubulin-binding domain.</p> "> Figure 2
<p>Schematic representation of the <span class="html-italic">S. cerevisiae</span> Glucose-Induced degradation Deficient (GID)- and correspondent mammalian CTLH-macromolecular complexes. (<b>A</b>) The topology of the GID complex in yeast is well established [<a href="#B31-ijms-19-01794" class="html-bibr">31</a>]; (<b>B</b>) Predicted composition of the mammalian CTLH complex based on the GID mammalian homologs. The name of the complex comes from the CTLH domain that most of the members have; (<b>C</b>) CTLH or Nuclear Receptor coregulator-complex pulled down from mammalian cells including RANBP9 and RANBP10 (adapted from [<a href="#B29-ijms-19-01794" class="html-bibr">29</a>]). In the depicted complex, GID8 is named C20orf11 and indicated as C20. The experiment showed as part of the complex also YPEL5 (<span class="underline">Y</span>ip<span class="underline">pe</span>e <span class="underline">L</span>ike 5) indicated as Y5 in the cartoon, which has no known equivalent in the <span class="html-italic">S. cerevisiae</span> GID complex.</p> "> Figure 3
<p>Potential action mechanism of RANBP9 in ATM-dependent DDR. In RANBP9 (red) expressing cells and in the absence of DNA damage (left panel, top), RANBP9 protein shuttles between the nucleus and the cytoplasm. Upon DNA damage such as IR and DNA-damaging drugs (left panel, bottom), ATM is activated and enhances RANBP9 nuclear accumulation through its phosphorylation, potentially with other cytoplasmic partners (purple). This event potentially leads to enhanced KAT5-dependent ATM acetylation, a marker of its full activation. For this reason, RANBP9-expressing cells activate an efficient ATM signaling pathway, resulting in efficient DNA repair and survival to genotoxic stress. Conversely, when RANBP9 expression is reduced, the full activation of ATM is impaired, leading to inefficient DNA repair and sensitivity to DNA damaging agents.</p> ">
Abstract
:1. Introduction
2. Scorpins
3. Known Biological Roles of RANBP9
4. RANBP9 in the DDR
4.1. RANBP9 and Sensitivity to Ionizing Radiation (IR)
4.2. RANBP9 and Post-Translational Modifications Following Stress
4.3. RANBP9 Protein-Protein Interactions Relevant to the DDR
4.4. RANBP9 as a Target and Signaling Facilitator of the Ataxia Telangiectasia Mutated (ATM) Kinase
4.5. RANBP9 as Pro-Apoptotic Tumor Suppressor
5. Known Biological Roles of RANBP10
6. RANBP10 in the DDR
7. Future Perspectives
Funding
Conflicts of Interest
References
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Protein Domain | Residue | AA | Target Peptide | PhosphoSitePlus | |
---|---|---|---|---|---|
RANBP9 (Uniprot Q96S59) | PRY | 181 | S | KFSYIGLSQNNLRVH | 1 |
LisH | 375 | S | MIQKMVSSYLVHHGY | - | |
CTLH | 426 | T | MGEAIETTQQLYPSL | - | |
Post-CTLH Region | 470 | S | LGGRSPKSQDSYPVS | 2 | |
483 | S | VSPRPFSSPSMSPSH | 58 | ||
550 | S | NSINMSRSQQVNNFT | 1 | ||
585 | S | NGFLNGSSKHDHEME | - | ||
603 | S | TEMEVDSSQLRRQLC | 2 | ||
613 | S | RRQLCGGSQAAIERM | 2 | ||
CRA | 631 | S | GRELQAMSEQLRRDC | - | |
705 | T | ALAMGQATQCLGLMA | - | ||
RANBP10 (Uniprot Q6VN20) | PRY | 69 | S | KYNYIGLSQGNLRVH | 1 |
LisH | 263 | S | VLQNMVSSYLVHHGY | - | |
CTLH | 314 | T | VGEAIETTQRFYPGL | - | |
Post-CTLH Region | 358 | S | LSSRSPKSQDSYPGS | 5 | |
365 | S | SQDSYPGSPSLSPRH | 160 | ||
377 | S | PRHGPSSSHMHNTGA | - | ||
386 | S | MHNTGADSPSCSNGV | 7 | ||
439 | S | NSTDSTKSQHHSSTS | - | ||
490 | S | DLQTDESSMDDRHPR | 13 | ||
CRA | 579 | S | LNSAILESQNLPKQP | - |
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Palmieri, D.; Tessari, A.; Coppola, V. Scorpins in the DNA Damage Response. Int. J. Mol. Sci. 2018, 19, 1794. https://doi.org/10.3390/ijms19061794
Palmieri D, Tessari A, Coppola V. Scorpins in the DNA Damage Response. International Journal of Molecular Sciences. 2018; 19(6):1794. https://doi.org/10.3390/ijms19061794
Chicago/Turabian StylePalmieri, Dario, Anna Tessari, and Vincenzo Coppola. 2018. "Scorpins in the DNA Damage Response" International Journal of Molecular Sciences 19, no. 6: 1794. https://doi.org/10.3390/ijms19061794