The nuclear factor kBeta (NF-kB) transcription factors or """"""""Rel"""""""" proteins have been the focus of intensive investigation because of their central role in multiple cell functions. Notably, an essential role of NF-kB transcription factors has recently been found in skeletal muscle atrophy. In classical NF-kB signaling, the inhibitor of kB (IkB) retains Rel heterodimers in the cytosol until it is phosphorylated by IkB kinase beta (IKKB) and subsequently degraded. IkB is decreased early and is sustained in atrophying muscle suggesting that its activating kinase, IKKB, could be involved in atrophy signaling. IKKB operates in a complex with IKKalpha (IKKa) and gamma. IKKa and IKKB are both protein kinases, but all three subunits work in concert to obtain maximum IKK activity. Since IKKa is required for function of the IKK complex and has been found to phosphorylate histone H3 promoting the expression of NF-kB target genes, IKK may very well also be involved in the NF-kB signaling required for muscle atrophy. Therefore, the overall aim of the proposed work is to determine the role of IKKa and IKKB in inactivity induced muscle atrophy. Determining the role of these kinases in atrophy could help provide therapies to combat skeletal muscle wasting. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AR054265-02
Application #
7449759
Study Section
Special Emphasis Panel (ZRG1-F10-H (21))
Program Officer
Boyce, Amanda T
Project Start
2006-07-06
Project End
2009-07-05
Budget Start
2007-07-06
Budget End
2008-07-05
Support Year
2
Fiscal Year
2007
Total Cost
$52,074
Indirect Cost
Name
Boston University
Department
Other Health Professions
Type
Schools of Allied Health Profes
DUNS #
049435266
City
Boston
State
MA
Country
United States
Zip Code
02215
Van Gammeren, Darin; Damrauer, Jeffrey S; Jackman, Robert W et al. (2009) The IkappaB kinases IKKalpha and IKKbeta are necessary and sufficient for skeletal muscle atrophy. FASEB J 23:362-70
Yokouchi, Mariko; Saleh, Marwah Adly; Kuroda, Keiko et al. (2009) Pathogenic epitopes of autoantibodies in pemphigus reside in the amino-terminal adhesive region of desmogleins which are unmasked by proteolytic processing of prosequence. J Invest Dermatol 129:2156-66