Date of Award
2023
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Biological Sciences
Committee Chair
Ahmed Lawan
Committee Member
Debra Moriarity
Committee Member
Joseph Ng
Subject(s)
Cell death, Phosphatases
Abstract
Senescence is a state of permanent cell cycle arrest which stops proliferation. It is hallmarked by changes in proteins such as p21, p53, and p16, which are regulated by mitogen-activated protein kinases (MAPKs) which are regulated by MAPK Phosphatases (MKPs). One such MKP, MKP-2, has a paucity of information on its physiological function. To study MKP-2 in senescence, we used mouse embryonic fibroblasts (MEFs) derived from novel MKP-2 whole-body knockout mice. These MEFs were analyzed using senescence-associated β-galactosidase assays and immunoblotting approaches. It was found that there were reduced β-Galactosidase positive cells and reduced senescence phenotypes in the Mkp2 -/- MEFs compared with Mkp2 +/+ MEFs. Furthermore, in UV-stimulated MEFs phosphorylated p53 was increased in the Mkp2 -/- MEFs compared with Mkp2 +/+ MEFs, along with alterations in phosphorylated ERK and p38 MAPK. It was also found that there was a decrease in p21 and p16 mRNA expression in the Mkp2 -/- MEFs that is associated with longer telomeres compared with Mkp2 +/+ MEFs. These results show that MKP-2 deficient MEFs are resistant to the development of cellular senescence.
Recommended Citation
Welch, Morgan, "The role of MKP-2 in cellular senescence and metabolic function" (2023). Theses. 457.
https://louis.uah.edu/uah-theses/457