Background:We showed that nuclear tyrosine phosphorylation is involved in chromatin structural changes. Results: Several tyrosine kinases phosphorylate KAP1 at Tyr-449, Tyr-458, and Tyr-517 in the nucleus, resulting in a decrease of KAP1 association with heterochromatin. Conclusion: Tyrosine phosphorylation of KAP1 by nucleus-localized tyrosine kinases, including Src, involves heterochromatin structural changes. Significance: These findings provide a new insight into nuclear tyrosine phosphorylation signals.

No abstract

Background: Tyrosine kinases are active in the cell nucleus and involved in global nuclear structure. Results: Phosphorylation of AKAP8 at multiple tyrosine residues by several nucleus-localized tyrosine kinases, including c-Src, induces AKAP8's dissociation from nuclear structures. Conclusion: Nuclear tyrosine phosphorylation of AKAP8 is involved in global nuclear structure changes. Significance: These findings highlight the importance of nuclear tyrosine phosphorylation in dynamic chromatin regulation.

Background: Mimosine is a cell synchronization reagent used for arresting cells in late G 1 and S phases. Results: Replication fork assembly is reversibly blocked by ATM activation through mimosine-generated reactive oxygen species. Conclusion: Mimosine induces cell cycle arrest strictly at the G 1 -S phase boundary, which prevents replication fork stallinginduced DNA damage. Significance: These findings provide a novel mechanism of the mimosine-induced G 1 checkpoint.

Proper resolution of inflammation is vital for repair and restoration of homeostasis after tissue damage, and its dysregulation underlies various noncommunicable diseases, such as cardiovascular and metabolic diseases. Macrophages play diverse roles throughout initial inflammation, its resolution, and tissue repair. Differential metabolic reprogramming is reportedly required for induction and support of the various macrophage activation states. Here we show that a long noncoding RNA (lncRNA),lncFAO, contributes to inflammation resolution and tissue repair in mice by promoting fatty acid oxidation (FAO) in macrophages.lncFAOis induced late after lipopolysaccharide (LPS) stimulation of cultured macrophages and in Ly6Chimonocyte-derived macrophages in damaged tissue during the resolution and reparative phases. We found thatlncFAOdirectly interacts with the HADHB subunit of mitochondrial trifunctional protein and activates FAO.lncFAOdeletion impairs resolution of inflammation related to endotoxic shock and delays resolution of inflammation and tissue repair in a skin wound. These results demonstrate that by tuning mitochondrial metabolism,lncFAOacts as a node of immunometabolic control in macrophages during the resolution and repair phases of inflammation.