Lamin A buffers CK2 kinase activity to modulate aging in a progeria mouse model.
Sci Adv
; 5(3): eaav5078, 2019 03.
Article
in En
| MEDLINE
| ID: mdl-30906869
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 CK2α 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 CK2α 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Progeria
/
Aging
/
Metalloendopeptidases
/
Lamin Type A
/
Casein Kinase II
/
Membrane Proteins
Limits:
Animals
/
Humans
Language:
En
Journal:
Sci Adv
Year:
2019
Document type:
Article
Affiliation country:
China
Country of publication:
Estados Unidos