Novel Cell-Penetrating Peptides Derived From Scaffold-Attachment- Factor A Inhibits Cancer Cell Proliferation and Survival

Pavan Kumar Puvvula; Anne M Moon

doi:10.3389/fonc.2021.621825

Novel Cell-Penetrating Peptides Derived From Scaffold-Attachment- Factor A Inhibits Cancer Cell Proliferation and Survival

Front Oncol. 2021 Mar 30:11:621825. doi: 10.3389/fonc.2021.621825. eCollection 2021.

Authors

Pavan Kumar Puvvula¹, Anne M Moon^{1

2

3}

Affiliations

¹ Department of Molecular and Functional Genomics, Weis Center for Research, Geisinger Clinic, Danville, PA, United States.
² Department of Human Genetics, University of Utah, Salt Lake City, UT, United States.
³ The Mindich Child Health and Development Institute, Hess Center for Science and Medicine at Mount Sinai, New York, NY, United States.

Abstract

Scaffold-attachment-factor A (SAFA) has important roles in many normal and pathologic cellular processes but the scope of its function in cancer cells is unknown. Here, we report dominant-negative activity of novel peptides derived from the SAP and RGG-domains of SAFA and their effects on proliferation, survival and the epigenetic landscape in a range of cancer cell types. The RGG-derived peptide dysregulates SAFA binding and regulation of alternatively spliced targets and decreases levels of key spliceosome proteins in a cell-type specific manner. In contrast, the SAP-derived peptide reduces active histone marks, promotes chromatin compaction, and activates the DNA damage response and cell death in a subset of cancer cell types. Our findings reveal an unprecedented function of SAFA-derived peptides in regulating diverse SAFA molecular functions as a tumor suppressive mechanism and demonstrate the potential therapeutic utility of SAFA-peptides in a wide range of cancer cells.

Keywords: RGG domain; SAP domain; cancer; cell-penetrating peptides; epigenetics; hnRNPU; splicing.