WW domains form a folded type of nuclear localization signal to guide YAP1 nuclear import.
J Cell Biol
; 223(6)2024 06 03.
Article
in En
| MEDLINE
| ID: mdl-38488622
ABSTRACT
The nuclear translocation of YAP1 is significantly implicated in the proliferation, stemness, and metastasis of cancer cells. Although the molecular basis underlying YAP1 subcellular distribution has been extensively explored, it remains to be elucidated how the nuclear localization signal guides YAP1 to pass through the nuclear pore complex. Here, we define a globular type of nuclear localization signal composed of folded WW domains, named as WW-NLS. It directs YAP1 nuclear import through the heterodimeric nuclear transport receptors KPNA-KPNB1, bypassing the canonical nuclear localization signal that has been well documented in KPNA/KPNB1-mediated nuclear import. Strikingly, competitive interference with the function of the WW-NLS significantly attenuates YAP1 nuclear translocation and damages stemness gene activation and sphere formation in malignant breast cancer cells. Our findings elucidate a novel globular type of nuclear localization signal to facilitate nuclear entry of WW-containing proteins including YAP1.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Nucleus
/
Nuclear Localization Signals
/
YAP-Signaling Proteins
Limits:
Humans
Language:
En
Journal:
J Cell Biol
Year:
2024
Document type:
Article
Country of publication: