P21 (P021)

"In biomedical research, the term ""P21"" refers to two fundamentally different bioactive molecules, which must be distinguished based on context:

1. p21 Waf1/Cip1 Protein and Its Derived Peptides: p21 is an endogenous cyclin-dependent kinase inhibitor protein encoded by the CDKN1A gene, playing a central role in cell cycle regulation, DNA damage repair, and apoptosis. Various p21-derived peptides have been designed. The most prominent is the C-terminal PCNA-interacting region (PIR) peptide of p21 (approximately 26 amino acids, corresponding to residues 139–164 of p21), containing the sequence GRKRRQTSMTDFYHSKRRLIFSKRKP, which competitively binds PCNA and simultaneously inhibits the recruitment of multiple translesion DNA synthesis (TLS) polymerases (S-Pols). Additionally, the p21-IRS chimeric peptide couples the p21 C-terminal domain with a cell-penetrating peptide (RYIRS), enabling rapid entry into lymphoid cells and activation of a non-classical apoptotic pathway.

2. PD-L1-Targeting Peptide-anti-miR-21 Conjugate (P21): This is a targeted delivery system formed by conjugating a PD-L1-binding peptide with an anti-miR-21 inhibitor via click chemistry, designed to precisely deliver anti-miR-21 to the PD-L1-high tumor microenvironment. By inhibiting oncogenic miR-21 in tumor cells and dendritic cells, this molecule activates the PTEN/AKT/mTOR pathway to induce autophagy and upregulates PDCD4 to trigger ER stress, ultimately leading to immunogenic cell death (ICD) and activation of anti-tumor immune responses."