The School of Molecular and Cellular Biology at the University of Illinois at Urbana-Champaign

Physiological balance is maintained, in part, through the rapid and well-timed assembly and disassembly of biological complexes. The dynamic interplay between select factors, which includes but is not limited to proteins and nucleic acids, facilitates an efficient and functional system. In general, pathways are driven forward through cooperative interactions, thereby providing important features for these systems—rapid and robust action with limited energy input. However, within multi-step systems cooperative stable assemblies may have a drawback since each complex would be recalcitrant to dissociation. Hence, transitions between functional complexes or termination of action would be slow unless catalyzed. Yet, the possible cellular actions that promote disassembly events are not well understood. A primary focus of our laboratory is to identify and comprehend the cellular components that mediate a dynamic protein environment.

The Freeman research group exploits two central nuclear processes, transcriptional regulation and telomere biology, as molecular paradigms to understand how the efficiency of a single system can impact homeostasis, as dysfunction of either can lead to cellular senescence or uncontrolled growth (i.e., cancer). Since both processes employ a number of factors with common binding specificities, a decline in pathway efficiency is highly plausible due to the misassembly of individual complexes or an impaired disassembly of structures. The fundamental properties of molecular chaperones (abundant proteins with promiscuous but weak binding activities) allow biological factors to avoid these challenges by cultivating a self-organizing environment, which allows a system to operate rapidly and efficiently. In essence, the ability of the chaperones to foster protein dynamics parallels the more established molecular chaperone roles in protein folding in which a chaperone does not dictate the final folded structure (path direction) but rather helps the nascent chain (system) avoid off-pathway energy barriers that commonly occur in protein folding (multi-step) energy landscapes. Our end goal is to understand the mechanisms by which molecular chaperones foster a dynamic protein system and how these actions contribute to homeostasis.

Representative Publications

Echtenkamp, F. J. and B. C. Freeman (2012) Expanding the Cellular Molecular Chaperone Network through the Ubiquitous Cochaperones. BBA - Molecular Cell Research, 45, 8624-8632. (ABSTRACT)

Echtenkamp, F. J., E. Zelin, E. Oxelmark, J. I. Woo, B. J. Andrews, M. J. Garabedian and B. C. Freeman (2011) Global Functional Map of the p23 Molecular Chaperone Reveals an Extensive Cellular Network. Mol. Cell, 43, 229-241. (ABSTRACT)

DeZwaan, D. C. and B. C. Freeman (2010) Hsp90 manages the ends. Trends Biochem. Sci., 7, 384-391. (ABSTRACT)

DeZwaan, D. C. and B. C. Freeman (2010) Is there a telomere-bound 'EST' telomerase holoenzyme? Cell Cycle., 7, 1913-1917. (ABSTRACT)

DeZwaan, D. C., O. A. Toogun, F. J. Echtenkamp and B. C. Freeman (2009) The Hsp82 molecular chaperone can promote the switch between unextendable and extendable telomere states. Nat. Struct. Mol. Biol., 16, 711 - 716. (ABSTRACT)

DeZwaan, D. C. and B. C. Freeman (2009) The conserved Est1 protein stimulates the telomerase reverse transcriptase. Proc. Nat.l Acad. Sci. USA, 106, 17337-17342. (ABSTRACT)

DeZwaan, D. C. and B. C. Freeman (2008) Hsp90: The Rosetta Stone of cellular protein dynamics? Cell Cycle., 7, 1006-1012. (ABSTRACT)

Toogun, O. A., D. C. DeZwaan, and B. C. Freeman (2008) The Hsp90 molecular chaperone modulates telomerase DNA binding and nucleotide processivity. Mol. Cell. Biol., 28, 457-467. (ABSTRACT)

Complete Publications List