- Pms2 and uracil-DNA glycosylases act jointly in the mismatch repair pathway to generate Ig gene mutations at A-T base pairs
Girelli Zubani et al. show that the Pms2 component of the mismatch repair complex and multiple uracil glycosylases contribute, each with a distinct strand bias, to enlarge the Ig gene mutation spectrum from G-C to A-T bases.
- Myeloid-derived cullin 3 promotes STAT3 phosphorylation by inhibiting OGT expression and protects against intestinal inflammation
Li et al. show that OGT-mediated STAT3 O-GlcNAcylation, which is modulated by CUL3-Nrf2 signaling, negatively regulates STAT3 phosphorylation and IL-10 production in macrophages and exacerbates experimental colitis and colitis-associated cancer.
- AKR1B1 promotes basal-like breast cancer progression by a positive feedback loop that activates the EMT program
The treatment of BLBC represents an unmet medical need. Wu et al. show that AKR1B1 facilitates BLBC progression through a positive feedback loop that activates the EMT program, suggesting that inhibition of AKR1B1 has the potential to become a valuable therapeutic strategy for BLBC.
- Inflammatory monocytes require type I interferon receptor signaling to activate NK cells via IL-18 during a mucosal viral infection
Although type I interferon is critical for NK cell activation, the underlying mechanism is under debate and is unknown during a mucosal infection. Lee et al. have determined that type I interferon induces inflammatory monocytes to produce IL-18 to directly activate NK cells to combat viral infections.
- Fumarate hydratase is a critical metabolic regulator of hematopoietic stem cell functions
Guitart et al. performed an in vivo genetic dissection of the Krebs cycle enzyme fumarate hydratase (Fh1) in the hematopoietic system. Their investigations revealed multifaceted functions of Fh1 in the regulation of hematopoietic stem cell biology and leukemic transformation.
- 27-Hydroxycholesterol impairs neuronal glucose uptake through an IRAP/GLUT4 system dysregulation
Ismail et al. show that 27-hydroxycholesterol, a peripheral cholesterol metabolite capable of passing the blood–brain barrier, reduces brain glucose uptake by upregulating the renin-angiotensin system and inhibiting GLUT4. This alteration affects memory processes and is likely to have implications on neurodegenerative diseases.
- RUNX1 cooperates with FLT3-ITD to induce leukemia
Behrens et al. establish the interplay of activated FLT3 receptor and the phosphorylated RUNX1 transcription factor in uncoupling proliferation and differentiation signals in acute leukemia. These findings demonstrate that RUNX1 is a viable therapeutic target in FLT3-mutated AML.
- Conserved IKAROS-regulated genes associated with B-progenitor acute lymphoblastic leukemia outcome
Analysis of mouse and human B lineage acute lymphoblastic leukemia identifies evolutionarily conserved targets of the tumor-suppressive transcription factor IKAROS, implicating CTNND1 in leukemia maintenance.
- Genetic analysis of Ikaros target genes and tumor suppressor function in BCR-ABL1+ pre–B ALL
Schjerven et al. compare mouse and human models of pre–B ALL to define conserved target genes and pathways of the tumor suppressor Ikaros, revealing CTNND1 and the early hematopoietic cell-surface receptors SPN (CD43) and CD34 as novel Ikaros targets that each confer oncogenic growth advantage.