hnRNPK-derived cell-penetrating peptide inhibits cancer cell survival

Discovery and characterization of anti-cancer peptides from a random peptide library

“…Our recent investigations on RBM39-RRM3-, SAFA-RGG- and hnRNPK-RGG- [ 3 , 22 , 23 ] derived cell-penetrating peptides revealed that treating cells with a penetratin-tagged peptide from these functional domains inhibited cancer cell growth and survival. This mode of action prompted us to develop a new unbiased technique to discover novel cell-penetrating peptides that could be developed therapeutically for use in various disease models.…”

“…We synthesized the six peptides with MDA-MB231 specific action ( Fig 2A and 2B ). Previously we showed that Penetratin-tagged synthetic peptides derived from known domains of three different RNA binding proteins efficiently enter T47D and MDA-MB231 breast cancer cells [ 3 , 22 , 23 ]. Here we examined penetration of these 6 novel random peptides into HCC1806 cells treated with 10μM peptide for 4 hours followed by immunofluorescence assay for the His tag ( S3A Fig ).…”

“…We previously demonstrated that RNA-binding domains of hnRNPK [ 22 ], hnRNPU [ 3 ], and RBM39 [ 23 ] act as dominant-negatives and reduce cancer cell growth and viability. However, identifying dominant-negative domains of potential therapeutic target proteins is a laborious process with no guarantee that they will have the desired cellular effect.…”

De Novo Single-Stranded RNA-Binding Peptides Discovered by Codon-Restricted mRNA Display

“… These developments suggest a wide range of potential applications for RBPs as versatile tools for biotechnological applications. For example, peptides originating from RNA-binding domains such as RBM39, SAFA, or hnRNPK have been conjugated with the Penetratin cell-penetrating peptide (CPP) to effectively inhibit cancer cell proliferation by disrupting RNA–protein interactions. , …”

“…For example, peptides originating from RNA-binding domains such as RBM39, SAFA, or hnRNPK have been conjugated with the Penetratin cell-penetrating peptide (CPP) to effectively inhibit cancer cell proliferation by disrupting RNA−protein interactions. 14,15 While nature has provided a repertoire of naturally occurring RBPs, these existing RBPs represent only a fraction of the potential repertoire of RBPs given a large fraction of the possible folds remains unexplored. 16 RNA-binding domains that remain unexplored in nature not only hold promise for the expansion of our biotechnological toolkit but also harbor the potential to deepen our understanding of the fundamental mechanisms governing these molecular interactions.…”