| University of Nevada
Biology Department m/s 314
Reno NV 89557
email Dr. Ardythe
A. McCracken
Office phone
775-784-6188
FAX number
775-784-1302
Dr. McCracken received her Ph.D. in Molecular Biology-Genetics
in 1981 with Arnold Clark at the University of Delaware and performed
her postdoctoral studies in protein biochemistry and secretion with
Jerry Brown at the University of Colorado Health Science Center;
she joined the Biology Department in 1987.
Dr. McCracken is not accepting new graduate students, but rather
is acting as student and faculty mentor to the department, visiting
professor at other Universities, and scientific advisor to foundations
and agencies.
Research:
Dr. McCracken’s research interests include the molecular biology
of intracellular protein trafficking and the underlying common principles
and mechanisms, with emphasis on the secretory pathway. Her recent
work has focused on understanding a quality control process that
ensures nascent proteins are correctly folded, processed, and completely
assembled before they exit the endoplasmic reticulum (ER) for further
transport through the secretory pathway. Most proteins that fail
to pass this checkpoint are degraded. Dr. McCracken and her colleagues
discovered the process by which these aberrant and unassembled secretory
proteins are removed from the ER, and named it ER-associated protein
degradation, or ERAD. A unique aspect of ERAD is that ER-lumenal
protein substrates are exported to the cytoplasm for degradation
by the proteasome complex. This discovery has far reaching significance
in that it reveals a cellular function for a retrograde protein
transporter in the ER, a mechanism implicated in the delivery of
cytotoxic proteins to the cytoplasm of the cell, and a transport
pathway exploited by the human cytomegalovirus to mask its presence
in infected cells. In addition, Dr. McCracken’s group recently
uncovered additional quality control pathways that appear to function
as overflow paths to the lysosome (vacuole) for the degradation
of aggregated protein. This discovery provides a possible explanation
for sporadic liver disease associated with deficiencies of at least
two plasma proteins and expands our understanding of the breadth
and complexity of cellular protein quality control.
Recent Publications:
Scott CM, Kruse KB, Schmidt BZ, Perlmutter DH, McCracken
AA, Brodsky JL. 2007. ADD66, a Gene Involved in the Endoplasmic
Reticulum Associated Degradation (ERAD) of Alpha-1-Antitrypsin-Z
in Yeast, Facilitates Proteasome Activity and Assembly. Mol Biol
Cell. Jul 18; [Epub ahead of print]
Palmer EA, Kruse KB, Fewell SW, Buchanan SM, Brodsky JL, McCracken
AA. 2003. Differential requirements of novel A1PiZ degradation
deficient (ADD) genes in ER-associated protein degradation. J Cell
Sci. 116:2361-73
McCracken AA, and Brodsky, JL. 2003. Evolving questions
and paradigm shifts in endoplasmic-reticulum-associated degradation
(ERAD). BioEssays 25:868-877
Lee RJ, Liu CW, Harty C, McCracken AA, Latterich
M, Romisch K, DeMartino GN, Thomas PJ, Brodsky JL. 2004. Uncoupling
retro-translocation and degradation in the ER-associated degradation
of a soluble protein. EMBO J. 23(11):2206-15
Lee, RJ, McCracken, AA, and Brodsky, JL. 2005.
Reconstitution of ER Associated Degradation (ERAD) using Yeast Membranes
and Cytosol. Methods Molecular Biology 301:175-184
Kruse, KB, Brodsky, JB, and McCracken, AA. 2006.
Characterization of an ERAD gene as VPS30/ATG6 reveals two alternative
and functionally distinct protein quality control pathways: Molecular
Biology Cell, 17:203-12
McCracken, AA and Brodsky, JL. 2006. Recognition
and delivery of ERAD substrates and alternative paths to cell survival.
In Dislocation and Degradation of Proteins from the Endoplasmic
Reticulum, Current Topics in Micro and Immunology, 300:17–40
Springer-Verlag Berlin Heidelberg
Kruse, KB, Brodsky, JB, and McCracken, AA. 2006.
Autophagy: an ER protein quality control process. Autophagy, 2:135-137
Kruse KB, Dear A, Kaltenbrun KB, Crum BE, George PM, Brennan SO,
and McCracken AA. 2006. Mutant fibrinogen cleared
from the ER via ERAD and autophagy: an explanation for liver disease.
American J Pathology, 168:1299-1308
Links:
Dr. McCracken Fulbright Scholarship announcement.
Dr. McCracken at Northern
Caribbean University as Fulbright Scholar
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