Designed novel nuclear localizing anticancer peptide targets p53 negative regulator MDM2 protein.
3D spheroid
HDM2/MDM2
nuclear localizing
p53
protein-protein interaction
Journal
Journal of peptide science : an official publication of the European Peptide Society
ISSN: 1099-1387
Titre abrégé: J Pept Sci
Pays: England
ID NLM: 9506309
Informations de publication
Date de publication:
Jan 2024
Jan 2024
Historique:
revised:
22
07
2023
received:
10
04
2023
accepted:
24
07
2023
medline:
11
12
2023
pubmed:
15
8
2023
entrez:
15
8
2023
Statut:
ppublish
Résumé
Intracellular protein-protein interactions provide a major therapeutic target for the development of peptide-based anticancer therapeutic agents. MDM2 is the 491-residue protein encoded by the MDM2 oncogene. Being a ubiquitin-protein ligase, MDM2 represses the transcription ability of the tumor suppressor p53 by proteasome-mediated degradation. Under typical cellular circumstances, a sustained p53 expression level is maintained by negative regulation of MDM2, whereas under stress conditions, this is alleviated to increase the p53 level. Modulation of MDM2-p53 interaction via fabrication of an MDM2-interacting peptide could be a useful strategy to inhibit subsequent proteasomal degradation of p53 and initiation of p53 signaling leading to the initiation of p53-mediated apoptosis of tumor cells. Here, in this research work, a novel anticancer peptide mPNC-NLS targeting the nucleus and the MDM2 protein (p53 negative regulator) was designed to promote the p53 protein activity for the prevention of cancer. It induces effective apoptosis in both A549 and U87 cells and remains non-cytotoxic to normal lung fibroblast cells (WI38). Further, immunocytochemistry and Western blot results confirm that the designed mPNC-NLS peptide induces the apoptotic death of lung cancer cells via activation of p53 and p21 proteins and remarkably stifled the in vitro growth of 3D multicellular spheroids composed of A549 cells.
Substances chimiques
Proto-Oncogene Proteins c-mdm2
EC 2.3.2.27
Tumor Suppressor Protein p53
0
Antineoplastic Agents
0
Peptides
0
MDM2 protein, human
EC 2.3.2.27
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3535Subventions
Organisme : Science and Engineering Research Board
ID : STR/2020/000048
Informations de copyright
© 2023 European Peptide Society and John Wiley & Sons Ltd.
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