Language
English
Publication Date
5-7-2024
Journal
Biochemistry
DOI
10.1021/acs.biochem.4c00056
PMID
38619104
PMCID
PMC12022813
PubMedCentral® Posted Date
4-25-2025
PubMedCentral® Full Text Version
Author MSS
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.
Keywords
NIMA-Interacting Peptidylprolyl Isomerase, Nanog Homeobox Protein, Phosphorylation, Humans, Protein Stability, Protein Binding, Stereoisomerism
Published Open-Access
yes
Recommended Citation
Ferreon, Josephine C; Ta, Hai Minh; Yun, Hyosuk; et al., "Stereospecific NANOG PEST Stabilization by Pin1" (2024). Faculty and Staff Publications. 3846.
https://digitalcommons.library.tmc.edu/baylor_docs/3846