Identification and Functional Characterizations of N-Terminal α-N-Methylation and Phosphorylation of Serine 461 in Human Poly(ADP-ribose) Polymerase 3
| Autor: | Stuart L. Rulten, Keith W. Caldecott, Yinsheng Wang, Xiaoxia Dai, Changjun You |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Methyltransferase
Poly ADP ribose polymerase Cell Cycle Proteins Biology Methylation Biochemistry Article Cell Line Serine chemistry.chemical_compound Tandem Mass Spectrometry Humans Amino Acid Sequence Phosphorylation Polymerase Kinase General Chemistry Molecular biology chemistry biology.protein Poly(ADP-ribose) Polymerases DNA |
| Zdroj: | Journal of Proteome Research. 14:2575-2582 |
| ISSN: | 1535-3907 1535-3893 |
| Popis: | Poly(ADP-ribose) polymerase 3 (PARP3) is a member of the PARP family enzymes which catalyze the ADP-ribosylation of proteins. PARP3 plays an important role in DNA damage repair and mitotic progression. In this study, we identified, using mass spectrometric techniques, two novel post-translational modification sites in PARP3, α-N-methylation and phosphorylation of serine 461 (S461). We found that the N-terminal α-amino group of PARP3 is heavily methylated in human cells, and N-terminal RCC1 methyltransferase (NRMT) is a key enzyme required for this methylation. We also observed that the phosphorylation level of S461 in PARP3 could be reduced in human cells upon treatment with flavopiridol, a cyclin-dependent kinase inhibitor. Moreover, we demonstrated that S461 phosphorylation, but not α-N-methylation of PARP3, may be involved in the cellular response toward DNA double-strand breaks. These findings provide novel insights into the post-translational regulation of PARP3. |
| Databáze: | OpenAIRE |
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