Targeting Cleavage of C-Terminal Fragment of Cytoskeletal Filamin A in Cancers.

Human cancers express altered levels of actin-binding cytoskeletal filamin A (FLNA) protein. FLNA in mammals consists of an actin-binding domain at its N-terminus that is followed by 24 immunoglobulin-like repeat modules interrupted by two hinge regions between repeats 15-16 and 23-24. Cleavage of these hinge regions produces a naturally occurring C-terminal 90 kDa fragment of FLNA (FLNACT) that physically interacts with multiple proteins with diverse functions. This cleavage leads to actin cytoskeleton remodeling, which in turn contributes to cellular signaling, nucleocytoplasmic shuttling of transcriptional factors and nuclear receptors, and regulation of their transcriptional activities that are important for initiation and progression of cancers. Therefore, recent studies have proposed blocking FLNA cleavage as a means of cancer therapy. Here, we update how FLNA cleavage has been targeted by different approaches and their potential implications for future treatment of human cancers.

Citation

Ozgur Cakici, Sashidar Bandaru, Grace Yankun Lee, Dyar Mustafa, Levent M Akyürek. Targeting Cleavage of C-Terminal Fragment of Cytoskeletal Filamin A in Cancers. Cells. 2024 Aug 21;13(16)

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PMID: 39195282

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