Structural Biology of the Human High Mobility Group A (HMGA) Proteins
EMSL Project ID
7794a
Abstract
HMGA1 proteins play a critical role in the adaptive immune response to infectious microorganisms and viruses, affecting gene regulation that stimulates resting lymphocytes into active T-cells by participating in transcriptional enhancer complexes known as enhanceosomes. In combination with other transcription factors, HMGA1 is an integral part of the enhanceosome structure, is essential to its function, and thus HMGA1 is key to induced expression of specific genes in response to specific antigens from infectious microorganisms. Because of its ubiquitous occurrence in a multitude of enhanceosomes, HMGA1 plays an important role, not only in immunology, but also in asthma, inflammation, atherosclerosis, arthritis, septic shock and cancer. With regards to cancer, HMGA1 has been shown to be an oncogene implicated in tumorigenesis and metastasis. Indeed, elevated levels of HMGA1 are strongly correlated with many cancers. Despite its important role in human health, very little is known about how HMGA1 is integrated into enhanceosome structure, how it might facilitate enhanceosome assembly, or how it might stimulate enhanceosome function. Because of its link to cancer, HMGA1 has emerged as a drug target for cross-linking agents designed to block misregulation of gene transcription in immortalized cancer cells. The structural studies proposed involving HMGA1 are designed to advance the understanding of the active role that HMGA1 plays in enhanceosome function and gene regulation.
Project Details
Project type
Capability Research
Start Date
2006-10-24
End Date
2008-09-19
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
"NMR resonance assignments of the human high mobility group protein HMGA1." Journal of Biomolecular NMR 38(2):185. Proposal ID: 7794, 7794a ERICA Product ID: 221558 Buchko GW, S Ni, NM Lourette, RC Reeves, and MA Kennedy. 2007.