PROGRESS REPORT AND UPDATED RESEARCH PLAN The main goal of this grant was to investigate the role of a transcriptional cofactor, GPS2, and its novel interacting partner, NEURL4/KIAA1787, in obesity-associated inflammatory responses and in the development of insulin resistance. Our original hypothesis was that these two proteins could play a key inhibitory role during the physiological response to insuHn signaling by keeping the NFKB and APi signaling network under negative control in the absence of stimulatory signals. The loss or downregulation of such inhibition may participate in the development of obesity-induced insulin resistance.
Three Specific Aims were proposed: i) To define GPS2-dependent gene networks in adipocytes;ii) To investigate the molecular mechanism of GPS2 and KIAA1787 functions in inhibiting JNK-mediated signaling and regulating transcriptional activation mediated by NFKB and APi transcription factors;iii) To test in vivo whether GPS2 and KIAA1787 are relevant for the development of insulin resistance by creating null mice models. Here, for each Aim, I will discuss the progresses made during the K99 phase of the award and describe the future experiments as the original plans have been updated in light ofthe current results.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Transition Award (R00)
Project #
7R00DK078756-04
Application #
8149970
Study Section
Special Emphasis Panel (NSS)
Program Officer
Margolis, Ronald N
Project Start
2010-09-25
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
4
Fiscal Year
2011
Total Cost
$246,511
Indirect Cost
Name
Boston University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Huang, Jiawen; Cardamone, M Dafne; Johnson, Holly E et al. (2015) Exchange Factor TBL1 and Arginine Methyltransferase PRMT6 Cooperate in Protecting G Protein Pathway Suppressor 2 (GPS2) from Proteasomal Degradation. J Biol Chem 290:19044-54
Cardamone, M Dafne; Tanasa, Bogdan; Chan, Michelle et al. (2014) GPS2/KDM4A pioneering activity regulates promoter-specific recruitment of PPAR?. Cell Rep 8:163-76
Cardamone, M Dafne; Krones, Anna; Tanasa, Bogdan et al. (2012) A protective strategy against hyperinflammatory responses requiring the nontranscriptional actions of GPS2. Mol Cell 46:91-104