Event Title

Molecular Evaluation of Transformation-Induced Methylation of the High Mobility Group A1 (HMGA1) Chromatin Binding Proteins

Poster Number

09

Presenter Information

Kendra Bufkin, Winthrop University

Faculty Mentor

Takita Sumter, Ph.D.

College

College of Arts and Sciences

Department

Chemistry, Physics and Geology

Location

Richardson Ballroom

Start Date

24-4-2015 1:20 PM

End Date

24-4-2015 2:50 PM

Description

Aberrant expression of high mobility group A1 (hmga1), resulting from inactivating defects in upstream tumor suppressor genes or upregulation of oncogenic transactivators, induces the initiation of cancer progression pathways. The protein products of hmga1, HMGA1a and HMGA1b, are characterized by the presence of three DNA-binding motifs that possess a central RGR sequence that plays a key role in preferential binding to the minor groove of AT-rich stretches of target DNA. Importantly, R25 of the RGR sequence within the first DNA-binding motif bears covalent modifications that may recruit or repel specific transcriptional regulators in cancer cells. Despite the implication of hmga1 and arginine methylation in oncogenic function, the role of epigenetic regulation of hmga1 by arginine methylation has not been evaluated. Here, we investigate the impact of R25 substitutions on HMGA1b binding DNA targets using fluorescence spectroscopy and functional cellular assays. R25 substitutions disrupt DNA binding to various targets and suppress HMGA1-dependent oncogenic transformation. Together, our data reveal new potential anti-cancer strategies by targeting HMGA1 protein methylation and downstream targets.

Comments

Kendra Bufkin is a McNair Scholar.

Presented at the Annual Meeting of the American Society for Biochemistry and Molecular Biology, March 2015

Supported by an NIH-INBRE grant from the National Center for Research Resources and the National Institute of General Medical Sciences; additional support provided by NIH-AREA and NSF-RIG grants, as well as a UAN Student Travel Award (ASBMB)

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Apr 24th, 1:20 PM Apr 24th, 2:50 PM

Molecular Evaluation of Transformation-Induced Methylation of the High Mobility Group A1 (HMGA1) Chromatin Binding Proteins

Richardson Ballroom

Aberrant expression of high mobility group A1 (hmga1), resulting from inactivating defects in upstream tumor suppressor genes or upregulation of oncogenic transactivators, induces the initiation of cancer progression pathways. The protein products of hmga1, HMGA1a and HMGA1b, are characterized by the presence of three DNA-binding motifs that possess a central RGR sequence that plays a key role in preferential binding to the minor groove of AT-rich stretches of target DNA. Importantly, R25 of the RGR sequence within the first DNA-binding motif bears covalent modifications that may recruit or repel specific transcriptional regulators in cancer cells. Despite the implication of hmga1 and arginine methylation in oncogenic function, the role of epigenetic regulation of hmga1 by arginine methylation has not been evaluated. Here, we investigate the impact of R25 substitutions on HMGA1b binding DNA targets using fluorescence spectroscopy and functional cellular assays. R25 substitutions disrupt DNA binding to various targets and suppress HMGA1-dependent oncogenic transformation. Together, our data reveal new potential anti-cancer strategies by targeting HMGA1 protein methylation and downstream targets.