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hnRNPK-derived cell-penetratingpeptide inhibits cancer cell survival by Pavan Kumar Puvvula; Stephanie Buczkowski; Anne M. Moon is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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hnRNPK is a multifunctional protein that plays an important role in cancer cell proliferation and metastasis via its RNA- and DNA-binding properties. Previously we showed that cell-penetrating peptides derived from the RGG RNA-binding domain of SAFA (hnRNPU) disrupt cancer cell proliferation and survival. Here we explore the efficacy of a peptide derived from the RGG domain of hnRNPK. This peptide acts in a dominant-negative manner on several hnRNPK functions to induce death of multiple types of cancer cells. The peptide phenocopies the effect of hnRNPK knockdown on its mRNA-stability targets such as __KLF4__ and __EGR1__ and alters the levels and locations of long non-coding RNAs (lncRNAs) and proteins required for nuclear and paraspeckle formation and function. The RGG-derived peptide also decreases euchromatin as evidenced by loss of active marks and polymerase II occupancy. Our findings reveal the potential therapeutic utility of the hnRNPK RGG-derived peptide in a range of cancers.

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Author

Pavan Kumar Puvvula; Stephanie Buczkowski; Anne M. Moon

Published

2021

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)