Date of Award
Master of Science (MS)
Cell death, Phosphatases
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.
Welch, Morgan, "The role of MKP-2 in cellular senescence and metabolic function" (2023). Theses. 457.
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