Exploring the Functional Interaction Between CaMK-II and p53

Calcium (Ca2+)/calmodulin-dependent kinase 2 (CaMK-II) is a multifunctional member of a family of Ca2+/calmodulin-dependent serine/threonine protein kinases that respond to transient intracellular calcium signaling. CaMK-II has been reported to be involved with transcription regulation, cell motility, neuronal development, cell cycle regulation, and more recently early development of vertebrates (Easley et al., 2008; Rothschild et al., 2009; Francescatto et al., 2010). Through previous work in the lab using tandem mass spectrometry and “substrate-trapping mutants”, tumor suppressor protein 53 (p53) was identified as a novel CaMK-II binding partner in tissue culture. In this study, I sought to provide characterization of the functional interaction of p53 and CaMK-II. First, a stable p53 knockdown human cell line (HEK) was established through lentiviral transduction of p53 shRNA and verified with immunoblots and immunostaining assays. Next, the localization of CaMK-II and the cell growth rate in these cells was determined. In wild type HEK cells, catalytically inactive CaMK-II inhibited cell growth, which is consistent with previous studies in mouse fibroblasts with pharmacological inhibition. p53-deficient cells were less sensitive to CaMK-II deficiencies using dominant negative CAMK-II, but not pharmacological disruption. The overall results of this study have provided significant clues to the mechanism between CaMK-II and p53 in the control of cell cycle progression.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Biology

Year dc:date.available

2011

Author dc:creator

• Lai, Raymond

Contributors dc:contributor

• Robert Tombes

• CaMK-II
• p53
• cell growth
• HEK
• mPCT
• Biology
• Life Sciences

Statement dc:rights

• © The Author

Identifier

https://scholarscompass.vcu.edu/etd/214

OAI identifier oai:identifier

oai:scholarscompass.vcu.edu:etd-1213