- Fh1 is essential for HSC 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.
- CTGF/CCN2 regulates myelination
One of the brain manifestations of tuberous sclerosis complex (TSC) is reduced myelination, but the underlying mechanism remains unclear. Ercan et al. demonstrate that mutant neurons overexpress a protein, connective tissue growth factor (CTGF), which impairs oligodendrocyte maturation and myelination.
- Ikaros tumor suppressor function in Ph+ 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.
- Conserved Ikaros-regulated genes in B-ALL
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.
- Skap2 in integrin activation
Boras et al. demonstrate that Skap2, via interaction with WASp, regulates actin polymerization and binding of talin-1 and kindlin-3 to the β2 integrin, thereby being indispensable for β2 integrin activation and neutrophil recruitment.
- RAG1/2 causes DNA insertions at independent breaks
Rommel et al. reveal a novel RAG1/2-mediated insertion pathway, which has the potential to destabilize the lymphocyte genome and shares features with DNA insertions observed in human cancer.
- Lipin-2 regulates NLRP3 inflammasome
Lordén et al. show that the phosphatidic acid phosphatase lipin-2 is a key regulator of the cellular machinery that generates IL-1β in macrophages. This work provides a molecular explanation for the development of the autoinflammatory disease known as Majeed syndrome.
- TRIM65 is required for MDA5 activation
Lang et al. identify E3 ligase TRIM65 as an essential component for the MDA-5 signaling pathway and provide solid evidence showing the importance of ubiquitination in MDA5 oligomerization and activation.
- NK cell survival during cell cycle
Natural killer (NK) cells eradicate virus-infected and transformed cells. Viant and colleagues describe the hierarchy of survival proteins and their apoptotic partners that govern NK cell survival. These data will inform approaches to harness NK cell activities in immunotherapies.