(Courtesy of Magda Stumpfova. Used with permission.)
Atrogin-1, a muscle-specific F-box
protein highly expressed during
muscle atrophy
M.D. Gomes, S.H. Lecker, R.T. Jagoe, A. Navon, and A.L. Goldberg
PNAS, Vol. 98, No. 25, Dec 4 2001, pg. 14440-14445
(Image removed due to copyright
considerations.)
See Case 109, Tetanus, at Pathology of Infectious Diseases, CD-Rom English
Version, by YUTAKA TSUTSUMI, M.D.
(http://www.yamagiku.co.jp/pathology/photo/
photo109-2.htm).
Background
Muscle packed with proteins
Serves as a primary reserve of amino acids for
Hepatic gluconeogenesis
Energy production
Fasting >>> increase in the Tx of ubiquitin
proteolysis related genes >>> increased
catalysis of muscle >>> muscle atrophy
www.yamagiku.co.jp/pathology/case/case109.htm
The point
What are the factors to affect the acceleration of muscle proteolysis in catabolic mode of the organism Establish a model of transcriptional adaptations during muscle atrophy that are responsible for the activation of muscle breakdown.
How did they go about identifying those factors
Image removed for copyright reasons. See http://www.u.arizona.edu/~gwatts/azcc/flowchart.gif.
 Isolation of gene, whose Tx significantly increased in atrophying muscle The protein it encodes fro was cloned + its properties described Analogous to E3 ligases of the SCF class but specific to striated muscle
Atrogin-1 protein
Source: Figure (1B), Gomes, M.D. et al. "Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy." Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14440-5. Epub 2001 Nov 20. Copyright 2001 National Academy of Sciences, U.S.A. Used with permission.
F-Box present at aa 228-267. Does it bind Skp1 protein
Should act as an adaptor between the proteins targeted for ubiquitination and the rests of the SCF complex. NLS present. Does it target nuclear proteins TF

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