Epigenetic Regulation of Cell-cycle Regulatory Proteins: A Multiple Myeloma Study
Standing
Undergraduate
Type of Proposal
Oral Research Presentation
Challenges Theme
Open Challenge
Faculty Sponsor
John Hudson, Lisa Porter, Dorota Lubanska
Proposal
Multiple Myeloma (MM) is a common hematopoietic cancer known to have an overaccumulation of malignant plasma cells in the bone marrow [1]. The coordination of crucial cell cycle proteins, such as mitotic and cyclin-dependent kinases, controls proper cell cycle progression during interphase and mitosis [2]. Polo-like kinases (PLKs) are a group of enzymes consisting of PLK1, PLK2, PLK 3, and PLK4 that play a vital role in the cell cycle regarding spindle-pole formation, centrosome maturation, and cytokinesis. Polo-like kinase (PLK) transcription is deregulated by promoter methylation, which causes protein-level changes linked to oncogenesis [3]. Cyclin dependent kinases are also responsible for proper cell cycle. A positive cell cycle regulator for enhanced cell proliferation is SpeedyA1 (Spy1). Spy1 binds to and activates Cdk2. Simultaneously, it promotes the degradation of p27Kip1, a Cdk inhibitor (CKI) [5]. Spy1 can also alter the substrate specificity of Cdk2 by increasing it to Spy1-Cdk2 than other Cyclin-Cdk2 complexes. Therefore, Spy1 could possibly contribute to aberrant cell division, resulting in tumorigenesis [5]. Our objective is to establish the methodology for methylation specific PCR (MSP) for PLK 1-PLK 4 and Spy1 proteins in U2-OS and Saos-2 cells grown in vitro [4]. After establishing an optimal protocol, we will characterize the methylation profile of these genes in Multiple Myeloma (MM) and normal bone marrow samples of patients. The PLK family has shown aberrant promoter methylation levels in ovarian cancer, glioblastoma, and cancer [3]. Similarly, Spy1 can suppress predominant stress responses in cells, including apoptosis, senescence, and DNA damage response pathways [6]. Therefore, altering the methylation status of Spy1 allows us to examine the role of this protein.
Grand Challenges
Viable, Healthy and Safe Communities
Epigenetic Regulation of Cell-cycle Regulatory Proteins: A Multiple Myeloma Study
Multiple Myeloma (MM) is a common hematopoietic cancer known to have an overaccumulation of malignant plasma cells in the bone marrow [1]. The coordination of crucial cell cycle proteins, such as mitotic and cyclin-dependent kinases, controls proper cell cycle progression during interphase and mitosis [2]. Polo-like kinases (PLKs) are a group of enzymes consisting of PLK1, PLK2, PLK 3, and PLK4 that play a vital role in the cell cycle regarding spindle-pole formation, centrosome maturation, and cytokinesis. Polo-like kinase (PLK) transcription is deregulated by promoter methylation, which causes protein-level changes linked to oncogenesis [3]. Cyclin dependent kinases are also responsible for proper cell cycle. A positive cell cycle regulator for enhanced cell proliferation is SpeedyA1 (Spy1). Spy1 binds to and activates Cdk2. Simultaneously, it promotes the degradation of p27Kip1, a Cdk inhibitor (CKI) [5]. Spy1 can also alter the substrate specificity of Cdk2 by increasing it to Spy1-Cdk2 than other Cyclin-Cdk2 complexes. Therefore, Spy1 could possibly contribute to aberrant cell division, resulting in tumorigenesis [5]. Our objective is to establish the methodology for methylation specific PCR (MSP) for PLK 1-PLK 4 and Spy1 proteins in U2-OS and Saos-2 cells grown in vitro [4]. After establishing an optimal protocol, we will characterize the methylation profile of these genes in Multiple Myeloma (MM) and normal bone marrow samples of patients. The PLK family has shown aberrant promoter methylation levels in ovarian cancer, glioblastoma, and cancer [3]. Similarly, Spy1 can suppress predominant stress responses in cells, including apoptosis, senescence, and DNA damage response pathways [6]. Therefore, altering the methylation status of Spy1 allows us to examine the role of this protein.