Title

Biophysical Characterization of the Full-Length Par-4 Tumor Suppressor

Description/Abstract

Tumor suppressor proteins are responsible for important cellular functions, such as DNA repair and cell apoptosis. The Prostate Apoptosis Response-4 (Par-4) tumor suppressor is encoded by the Par-4/ PaWR gene found in chromosome 12q21.2. The 38 kilodalton full-length Par-4 (FL)-Par-4 has been shown to induce cell apoptosis in response to various stimuli in different cellular systems. However, FL-Par-4 protein is intrinsically disordered under neutral conditions in vitro. Par-4 translocates into the nucleus for cell apoptosis induction only after it is cleaved by the caspase-3 at aspartic acid 131. The reason for this cleavage requirement has not yet been determined. Our previous research with the caspase-3-cleaved fragment (cl- Par-4) have shown that ordered protein structure can be induced by either acidic conditions or by a high concentration of monovalent cations. In this study, we are investigating whether similar conditions also induce structure into (FL) Par-4. Determining FL Par-4 structure will enhance our understanding of structural similarities and differences between the FL Par-4 and cl-Par-4 fragment. Preliminary circular dichroism (CD) data of FL Par-4 show that both monovalent and divalent cations do affect the degree of structure in FL-Par-4. Additional techniques, such as tyrosine fluorescence, size exclusion chromatography with multi angle scattering (SEC-MALS), and dynamic light scattering (DLS) will also be used to characterize FL Par-4 structure under various conditions. These results will increase our understanding of Par-4 structure in relation to the cellular environment and how cleavage alters Par-4 structure, including the ability of Par-4 to be induced to fold via various stimuli.

Presenting Author Name/s

Christiana Ntangka

Faculty Advisor

Steven M. Pascal

Presentation Type

Poster

Disciplines

Biochemistry, Biophysics, and Structural Biology

Session Title

Poster Session

Location

Learning Commons, Atrium

Start Date

2-8-2020 8:00 AM

End Date

2-8-2020 12:30 PM

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Feb 8th, 8:00 AM Feb 8th, 12:30 PM

Biophysical Characterization of the Full-Length Par-4 Tumor Suppressor

Learning Commons, Atrium

Tumor suppressor proteins are responsible for important cellular functions, such as DNA repair and cell apoptosis. The Prostate Apoptosis Response-4 (Par-4) tumor suppressor is encoded by the Par-4/ PaWR gene found in chromosome 12q21.2. The 38 kilodalton full-length Par-4 (FL)-Par-4 has been shown to induce cell apoptosis in response to various stimuli in different cellular systems. However, FL-Par-4 protein is intrinsically disordered under neutral conditions in vitro. Par-4 translocates into the nucleus for cell apoptosis induction only after it is cleaved by the caspase-3 at aspartic acid 131. The reason for this cleavage requirement has not yet been determined. Our previous research with the caspase-3-cleaved fragment (cl- Par-4) have shown that ordered protein structure can be induced by either acidic conditions or by a high concentration of monovalent cations. In this study, we are investigating whether similar conditions also induce structure into (FL) Par-4. Determining FL Par-4 structure will enhance our understanding of structural similarities and differences between the FL Par-4 and cl-Par-4 fragment. Preliminary circular dichroism (CD) data of FL Par-4 show that both monovalent and divalent cations do affect the degree of structure in FL-Par-4. Additional techniques, such as tyrosine fluorescence, size exclusion chromatography with multi angle scattering (SEC-MALS), and dynamic light scattering (DLS) will also be used to characterize FL Par-4 structure under various conditions. These results will increase our understanding of Par-4 structure in relation to the cellular environment and how cleavage alters Par-4 structure, including the ability of Par-4 to be induced to fold via various stimuli.