| First Author | Shi Y | Year | 2024 |
| Journal | Sci Adv | Volume | 10 |
| Issue | 38 | Pages | eado4274 |
| PubMed ID | 39303038 | Mgi Jnum | J:354884 |
| Mgi Id | MGI:7732578 | Doi | 10.1126/sciadv.ado4274 |
| Citation | Shi Y, et al. (2024) Cancer-associated SF3B1-K700E mutation controls immune responses by regulating T(reg) function via aberrant Anapc13 splicing. Sci Adv 10(38):eado4274 |
| abstractText | Recurrent somatic mutations in spliceosome factor 3b subunit 1 (SF3B1) are identified in hematopoietic malignancies, with SF3B1-K700E being the most common one. Here, we show that regulatory T cell (T(reg))-specific expression of SF3B1-K700E (Sf3b1(K700Efl/+)/Foxp3(YFP-Cre)) results in spontaneous autoimmune phenotypes. CD4(+) T cells from Sf3b1(K700Efl/+)/Foxp3(YFP-Cre) mice display defective T(reg) differentiation and inhibitory function, which is demonstrated by failed prevention of adoptive transfer colitis by Sf3b1(K700Efl/+)/Foxp3(YFP-Cre) T(regs). Mechanically, SF3B1-K700E induces an aberrant splicing event that results in reduced expression of a cell proliferation regulator Anapc13 due to the insertion of a 231-base pair DNA fragment to the 5' untranslated region. Forced expression of the Anapc13 gene restores the differentiation and ability of Sf3b1(K700Efl/+)/Foxp3(YFP-Cre) T(regs) to prevent adoptive transfer colitis. In addition, acute myeloid leukemia grows faster in aged, but not young, Sf3b1(K700Efl/+)/Foxp3(YFP-Cre) mice compared to Foxp3(YFP-Cre) mice. Our results highlight the impact of cancer-associated SF3B1 mutation on immune responses, which affect cancer development. |
