Polypyrimidine tract-binding protein 1 (PTBP1) (PTBP1)

Polypyrimidine tract-binding protein 1 (PTBP1) is a multifunctional RNA-binding protein and a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family that plays a pivotal role in post-transcriptional gene regulation (UniProt P26599). It primarily functions as a splicing repressor, but also influences mRNA stability, transport, and internal ribosome entry site (IRES)-mediated translation (PubMed: 22033518). In the context of the TNF-α/NF-κB signaling pathway, PTBP1 has been shown to stabilize transcripts of key pathway components or modulate the splicing of downstream effectors, thereby promoting inflammatory responses and oncogenic progression in various cancers (PubMed: 32503417). PTBP1 is frequently upregulated in malignancies such as colorectal cancer and glioma, where it facilitates the metabolic switch to aerobic glycolysis by favoring the splicing of the PKM2 isoform (PubMed: 26159100). Beyond oncology, PTBP1 is a significant target in regenerative medicine due to findings that its depletion can trigger the conversion of astrocytes into functional neurons, offering a potential therapeutic avenue for neurodegenerative diseases like Parkinson's (PubMed: 32581358). While no small-molecule inhibitors are currently approved, experimental approaches using antisense oligonucleotides (ASOs) and RNA interference are being actively explored to modulate its activity in disease states.

Other names

PTBhnRNP IHNRNPIPolypyrimidine tract-binding proteinPTB-1

Inhibition of PTBP1 modulates the alternative splicing and stability of mRNAs involved in the TNF-α/NF-κB signaling cascade, leading to reduced expression of pro-inflammatory and pro-survival factors (PubMed: 32503417).