SETD1A function in leukemia is mediated through interaction with mitotic regulators BuGZ/BUB3 Journal Article
| Authors: | Perlee, S.; Kikuchi, S.; Nakadai, T.; Masuda, T.; Ohtsuki, S.; Matsumoto, M.; Rahmutulla, B.; Fukuyo, M.; Cifani, P.; Kentsis, A.; Roeder, R. G.; Kaneda, A.; Hoshii, T. |
| Article Title: | SETD1A function in leukemia is mediated through interaction with mitotic regulators BuGZ/BUB3 |
| Abstract: | The H3K4 methyltransferase SETD1A plays a crucial role in leukemia cell survival through its noncatalytic FLOS domain-mediated recruitment of cyclin K and regulation of DNA damage response genes. In this study, we identify a functional nuclear localization signal in and interaction partners of the FLOS domain. Our screen for FLOS domain-binding partners reveals that the SETD1A FLOS domain binds mitosis-associated proteins BuGZ/BUB3. Inhibition of both cyclin K and BuGZ/BUB3-binding motifs in SETD1A shows synergistic antileukemic effects. BuGZ/BUB3 localize to SETD1A-bound promoter-TSS regions and SETD1A-negative H3K4me1-positive enhancer regions adjacent to SETD1A target genes. The GLEBS motif and intrinsically disordered region of BuGZ are required for both SETD1A-binding and leukemia cell proliferation. Cell-cycle-specific SETD1A restoration assays indicate that SETD1A expression at the G1/S phase of the cell cycle promotes both the expression of DNA damage response genes and cell cycle progression in leukemia cells. © 2023 The Authors. |
| Keywords: | leukemia; genetics; mitosis; cell cycle protein; metabolism; cell cycle proteins; cell cycle; dna repair; transcription; cycline; cyclins; humans; human; poly adp ribose binding protein; poly-adp-ribose binding proteins; setd1a; bugz; bub3 protein, human |
| Journal Title: | EMBO Reports |
| Volume: | 24 |
| Issue: | 10 |
| ISSN: | 1469-221X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2023-10-09 |
| Start Page: | e57108 |
| Language: | English |
| DOI: | 10.15252/embr.202357108 |
| PUBMED: | 37535603 |
| PROVIDER: | scopus |
| PMCID: | PMC10561176 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- Source: Scopus |
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