Abstract
Profilin-1 (PFN1) regulates actin polymerization and cytoskeletal growth. Despite the essential roles of PFN1 in cell integration, its subcellular function in keratinocyte has not been elucidated yet. Here we characterize the specific regulation of PFN1 in DNA damage response and repair machinery. PFN1 depletion accelerated DNA damage-mediated apoptosis exhibiting PTEN loss of function instigated by increased phosphorylated inactivation followed by high levels of AKT activation. PFN1 changed its predominant cytoplasmic localization to the nucleus upon DNA damage and subsequently restored the cytoplasmic compartment during the recovery time. Even though γH2AX was recruited at the sites of DNA double strand breaks in response to DNA damage, PFN1-deficient cells failed to recruit DNA repair factors, whereas control cells exhibited significant increases of these genes. Additionally, PFN1 depletion resulted in disruption of PTEN-AKT cascade upon DNA damage and CHK1-mediated cell cycle arrest was not recovered even after the recovery time exhibiting γH2AX accumulation. This might suggest PFN1 roles in regulating DNA damage response and repair machinery to protect cells from DNA damage. Future studies addressing the crosstalk and regulation of PTEN-related DNA damage sensing and repair pathway choice by PFN1 may further aid to identify new mechanistic insights for various DNA repair disorders.
Highlights
Skin is a primary barrier to detrimental circumstance such as UV and chemical attack
Profilin catalyzes the exchanges of ADP to ATP of globular actin (G-actin) and it leads to ready state of actin nucleation at barbed end of filamentous actin (F-actin) [6]
For the highlighted comparison between EV- and shPFN1-transduced groups at 12 h of recovery time after 1 h of DOX exposure, numbers for apoptosis are boxed in blue and for G0/G1 in red Cytoskeleton is essential for cell survival, motility and differentiation and its disruption is one of the most distinct features observed in various diseases [34, 35]
Summary
Skin is a primary barrier to detrimental circumstance such as UV and chemical attack. Especially keratinocytes in epithelial layer, undergo dynamic changes in response to DNA damage, and a single DNA breakage can be lethal leading to malignant transformation if it remains unrepaired, or aberrantly repaired. Profilins are composed of four isoforms and among these family Profilin (PFN1) is the most widely expressed and studied gene emphasizing its roles as a component of actin assembly. Dysregulation of PFN1 induces actin cytoskeleton-associated alterations such as cell proliferation, migration and adhesion with morphological changes [7,8,9]. In this study we firstly characterized the functional roles of PFN1 in human keratinocytes and its specific regulation in DNA damage response and repair machinery
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
