The major goal of the Perissi lab is to investigate the transcriptional and non-transcriptional functions of various cofactors with a particular focus on their misregulation during disease states such as cancer, diabetes and other inflammatory disorders. We have been interested for a long time in the regulation of transcriptional events by corepressor and coactivator complexes and in particular we have focused on the NCoR/SMRT corepressors and its associated proteins HDAC3, TBL1 and TBLR1. More recently, based on the finding that another component of the same complex, GPS2, was required for the adipogenic differentiation of 3T3-L1 cells, we began investigating the mechanism of its actions in adipogenesis and uncovered a critical, non-transcriptional role for GPS2 in regulating the enzymatic activity of the TRAF2/CIAP1/Ubc13 ubiquitin conjugating complex and therefore inhibiting the pro-inflammatory TNFalpha pathway. Our goal now is to investigate, both in vitro and in vivo, in tissue-specific mouse models, how the different components of the NCoR complex contribute to broadly regulate the cellular responses to external stimulation by acting in different cellular compartments to modulate hormonal and inflammatory pathways. Ongoing projects aim at: i) determining GPS2 role in the regulation of K63 ubiquitin chain formation within inflammatory responses regulated by Toll-like receptors and TNFalpha in macrophages and B-cells; ii) dissecting the molecular mechanism of GPS2 role in nuclear receptor-mediated transcriptional regulation in differentiating and mature adipocytes; iii) understanding how GPS2 sub-cellular localization and specific functions are regulated by post-translational modifications in different cell types.
Please contact Dr. Perissi by e-mail for more information about open positions for postdoctoral fellows and graduate students.
Signal Transduction and Cancer
- University of California, San Diego, PhD
- Published on 3/1/2018
Cardamone MD, Tanasa B, Cederquist CT, Huang J, Mahdaviani K, Li W, Rosenfeld MG, Liesa M, Perissi V. Mitochondrial Retrograde Signaling in Mammals Is Mediated by the Transcriptional Cofactor GPS2 via Direct Mitochondria-to-Nucleus Translocation. Mol Cell. 2018 Mar 01; 69(5):757-772.e7. PMID: 29499132.
- Published on 5/24/2017
Mahdaviani K, Benador IY, Su S, Gharakhanian RA, Stiles L, Trudeau KM, Cardamone M, Enríquez-Zarralanga V, Ritou E, Aprahamian T, Oliveira MF, Corkey BE, Perissi V, Liesa M, Shirihai OS. Mfn2 deletion in brown adipose tissue protects from insulin resistance and impairs thermogenesis. EMBO Rep. 2017 Jul; 18(7):1123-1138. PMID: 28539390.
- Published on 12/30/2016
Lentucci C, Belkina AC, Cederquist CT, Chan M, Johnson HE, Prasad S, Lopacinski A, Nikolajczyk BS, Monti S, Snyder-Cappione J, Tanasa B, Cardamone MD, Perissi V. Inhibition of Ubc13-mediated Ubiquitination by GPS2 Regulates Multiple Stages of B Cell Development. J Biol Chem. 2017 Feb 17; 292(7):2754-2772. PMID: 28039360.
- Published on 10/31/2016
Cederquist CT, Lentucci C, Martinez-Calejman C, Hayashi V, Orofino J, Guertin D, Fried SK, Lee MJ, Cardamone MD, Perissi V. Systemic insulin sensitivity is regulated by GPS2 inhibition of AKT ubiquitination and activation in adipose tissue. Mol Metab. 2017 Jan; 6(1):125-137. PMID: 28123943.
- Published on 6/12/2015
Huang J, Cardamone MD, Johnson HE, Neault M, Chan M, Floyd ZE, Mallette FA, Perissi V. Exchange Factor TBL1 and Arginine Methyltransferase PRMT6 Cooperate in Protecting G Protein Pathway Suppressor 2 (GPS2) from Proteasomal Degradation. J Biol Chem. 2015 Jul 31; 290(31):19044-54. PMID: 26070566.
- Published on 6/19/2014
Cardamone MD, Tanasa B, Chan M, Cederquist CT, Andricovich J, Rosenfeld MG, Perissi V. GPS2/KDM4A pioneering activity regulates promoter-specific recruitment of PPAR?. Cell Rep. 2014 Jul 10; 8(1):163-76. PMID: 24953653.
- Published on 5/17/2013
Scafoglio C, Smolka M, Zhou H, Perissi V, Rosenfeld MG. The co-repressor SMRT delays DNA damage-induced caspase activation by repressing pro-apoptotic genes and modulating the dynamics of checkpoint kinase 2 activation. PLoS One. 2013; 8(5):e59986. PMID: 23690919.
- Published on 3/15/2012
Cardamone MD, Krones A, Tanasa B, Taylor H, Ricci L, Ohgi KA, Glass CK, Rosenfeld MG, Perissi V. A protective strategy against hyperinflammatory responses requiring the nontranscriptional actions of GPS2. Mol Cell. 2012 Apr 13; 46(1):91-104. PMID: 22424771.
- Published on 2/1/2010
Perissi V, Jepsen K, Glass CK, Rosenfeld MG. Deconstructing repression: evolving models of co-repressor action. Nat Rev Genet. 2010 Feb; 11(2):109-23. PMID: 20084085.
- Published on 7/10/2009
Huang W, Ghisletti S, Perissi V, Rosenfeld MG, Glass CK. Transcriptional integration of TLR2 and TLR4 signaling at the NCoR derepression checkpoint. Mol Cell. 2009 Jul 10; 35(1):48-57. PMID: 19595715.
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