Stereospecific NANOG PEST Stabilization by Pin1.
Biochemistry
; 63(9): 1067-1074, 2024 May 07.
Article
en En
| MEDLINE
| ID: mdl-38619104
ABSTRACT
NANOG protein levels correlate with stem cell pluripotency. NANOG concentrations fluctuate constantly with low NANOG levels leading to spontaneous cell differentiation. Previous literature implicated Pin1, a phosphorylation-dependent prolyl isomerase, as a key player in NANOG stabilization. Here, using NMR spectroscopy, we investigate the molecular interactions of Pin1 with the NANOG unstructured N-terminal domain that contains a PEST sequence with two phosphorylation sites. Phosphorylation of NANOG PEST peptides increases affinity to Pin1. By systematically increasing the amount of cis PEST conformers, we show that the peptides bind tighter to the prolyl isomerase domain (PPIase) of Pin1. Phosphorylation and cis Pro enhancement at both PEST sites lead to a 5-10-fold increase in NANOG binding to the Pin1 WW domain and PPIase domain, respectively. The cis-populated NANOG PEST peptides can be potential inhibitors for disrupting Pin1-dependent NANOG stabilization in cancer stem cells.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Peptidilprolil Isomerasa de Interacción con NIMA
/
Proteína Homeótica Nanog
Límite:
Humans
Idioma:
En
Revista:
Biochemistry
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos