Laboratory of Arthur L. Haas, PhD
The LSU School of Medicine and LSU Health Sciences Center are pleased to announce the establishment of the Arthur L. Haas Endowed Lectureship. An anonymous donor made a $100,000 gift to fund this lectureship in honor of Dr. Haas’ illustrious career in research, mentoring, and academic leadership and to support higher education within the School’s membership and the New Orleans public. read more...
Graduate Training: Northwestern University School of Medicine, 1979; Post-doctoral Training: Institute for Cancer Research
of the Fox Chase Cancer Center, Philadelphia, Pennsylvania.
Haas Lab Photo: Virginia Ronchi, Dustin Todaro, Art Haas, Jenny Klein, Elizabeth Kim
Ubiquitin is a highly conserved 8600 dalton polypeptide distributed throughout eukaryotes. The biological effects of ubiquitin are exerted through a unique post-translational modification in which the polypeptide is covalently ligated to free amino groups on various intracellular target proteins in an ATP-coupled reaction.
The end result of ubiquitination is degradation of the target protein by the 26S proteasome complex, a large (2MDa) multisubunit complex which recognises multi-ubiquitinated proteins and degrades them to small peptides. The ubiquitin chain is released and is broken up into single ubiqutin molecules which are then reused.
The major role of ubiquitin conjugation is in targeting proteins for degradation as an essential regulatory step. Other roles for which conjugation has been implicated include gene regulation, DNA repair, stress response, cell cycle progression, various forms of muscle atrophy, and Alzheimers dementia.
We have also identified a second constitutive system within cells that is parallel but distinct from ubiquitin in which the 15 kDa interferon-like protein ISG15/UCRP is conjugated to a smaller subset of intracellular targets. ISG15 is the archetype of a small group of function-specific ubiquitin-like proteins that includes SUMO-1 and Nedd8. The conjugation of ISG15 to intracellular targets functions to regulate protein-protein interactions, in one instance acting in trans to mediate association of the target with intermediate filaments.
The general areas of work for both systems involve:
- Identification,purification, and enzymological characterization of enzymes involved in the respective conjugation reactions
- Use of site-directed mutagenesis to dissect the mechanisms of conjugation
- Studies examining the roles of ubiquitin and ISG15 conjugation in cellular regulation
- Exploitation of recent proteomic methods to identify targets for ISG15 conjugation.
Ubiquitin is a small, 76 amino acid protein, which becomes covalently attached to other proteins via an isopeptide bond from Gly76 (green) of ubiquitin to the epsilon amino group of a lysine on the target protein. Ubiquitin Lysine48 is shown in blue.
If you are using a browser with the Chime plugin, click here to see a model of ubiquitin that you can manipulate in 3D.
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