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

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 proliferat...

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Bibliographic Details
Published in:Frontiers in oncology 2021-03, Vol.11, p.621825-621825
Main Authors: Puvvula, Pavan Kumar, Moon, Anne M
Format: Article
Language:English
Subjects:
cancer
cell-penetrating peptides
epigenetics
hnRNPU
Oncology
RGG domain
splicing
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Summary: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.
ISSN:2234-943X
2234-943X
DOI:10.3389/fonc.2021.621825