| First Author | Ao Y | Year | 2019 |
| Journal | Sci Adv | Volume | 5 |
| Issue | 3 | Pages | eaav5078 |
| PubMed ID | 30906869 | Mgi Jnum | J:288441 |
| Mgi Id | MGI:6432225 | Doi | 10.1126/sciadv.aav5078 |
| Citation | Ao Y, et al. (2019) Lamin A buffers CK2 kinase activity to modulate aging in a progeria mouse model. Sci Adv 5(3):eaav5078 |
| abstractText | Defective nuclear lamina protein lamin A is associated with premature aging. Casein kinase 2 (CK2) binds the nuclear lamina, and inhibiting CK2 activity induces cellular senescence in cancer cells. Thus, it is feasible that lamin A and CK2 may cooperate in the aging process. Nuclear CK2 localization relies on lamin A and the lamin A carboxyl terminus physically interacts with the CK2alpha catalytic core and inhibits its kinase activity. Loss of lamin A in Lmna-knockout mouse embryonic fibroblasts (MEFs) confers increased CK2 activity. Conversely, prelamin A that accumulates in Zmpste24-deficent MEFs exhibits a high CK2alpha binding affinity and concomitantly reduces CK2 kinase activity. Permidine treatment activates CK2 by releasing the interaction between lamin A and CK2, promoting DNA damage repair and ameliorating progeroid features. These data reveal a previously unidentified function for nuclear lamin A and highlight an essential role for CK2 in regulating senescence and aging. |
