Hyaluronan‐binding protein 1 (HABP1) overexpression triggers induction of senescence in fibroblasts cells. (28th February 2020)

• Record Type: Journal Article
• Authors: Vikramdeo, Kunwar Somesh; Saha, Paramita; Dutta, Shubhra; Kumar, Naveen; Roy Chowdhury, Anindya; Kumar, Sudhir; Tyagi, Rakesh Kumar; Ghosh, Ilora; Datta, Kasturi
• Is Part Of: Cell biology international. Volume 44:Number 6(2020)
• Page Start: 1312
• Page End: 1330
• Publication Date: 2020-02-28
• Subjects: F‐HABP07 -- HABP1 -- IQGAP1 -- senescence; Cytology -- Periodicals; Cells -- Periodicals; 571.605
• DOI: 10.1002/cbin.11326
• Languages: English
• ISSNs: 1065-6995

Abstract

Abstract: Hyaluronan‐binding protein 1 (HABP1), a multi‐compartmental, multi‐functional protein has a wide range of functions, which can be attributed to its ability to associate with a variety of cellular ligands. Earlier we have reported that HABP1 overexpression in rat normal fibroblasts (F‐HABP07) shows chronic generation of reactive oxygen species (ROS), induction of autophagy, and apoptosis. However, a significant proportion of cells remained viable after the majority went through apoptosis from 60 to 72 h. In this study, an attempt has been made to delineate the cellular events in the declined population of surviving cells. It has been elucidated here that, these cells at later time points of growth, that is, 72 and 84 h, not only appeared to shrink but also are devoid of autophagic vacuoles and displayed polyploidy. F‐HABP07 cells exhibited an altered cytoskeletal structure from their parental cell line F111, assumed to be caused upon inhibition of actin polymerization and decrease in IQ motif‐containing GTPase activating protein 1 (IQGAP1), a key protein associated with maintenance of cytoskeletal integrity. Enhanced expression and nuclear localization of AKT observed in F‐HABP07 cells appears to be contributing toward the maintenance of high ROS levels in these cells and also potentially modulating the IQGAP1 activity. These observations, in fact have been considered to result in sustained DNA damage, which then leads to increased expression of p53 and activation of p21 and carry out the cellular events responsible for senescence. Subsequent assessment of the presence of positive β‐gal staining and enhanced expression of p16 INK4a in F‐HABP07, confirmed that HABP1 overexpressing fibroblasts undergo senescence.