CARMA1 coiled-coil domain is involved in the oligomerization and subcellular localization of CARMA1 and is required for T cell receptor-induced NF-kappaB activation.
T lymphocyte (T cell) activation and proliferation is induced by the activation of multiple signal transduction pathways. Earlier studies indicate that CARMA1, a Caspase Recruitment Domain (CARD) and Membrane-associated GUanylate Kinase domain (MAGUK)-containing scaffold protein, plays an essential role in NF-kappaB activation induced by the costimulation of T cell receptor (TCR) and CD28 molecules. However, the molecular mechanism by which CARMA1 mediates TCR-CD28 costimulation-induced NF-kappaB activation is not fully understood. Here we show that CARMA1 is constitutively oligomerized. This oligomerization of CARMA1 is through its Coiled-coil domain. Disruption of the predicted structure of the Coiled-coil domain of CARMA1 impaired its oligomerization and, importantly, abrogated CARMA1-mediated NF-kappaB activation. Interestingly, disruption of the CC1 domain abrogates CARMA1 localization, whereas disruption of the CC2 domain seems to inhibit CARMA1 self-association. Together, our results demonstrate that the oligomerization of CARMA1 is required for TCR-induced NF-kappaB activation.
Tanner
Matthew J
MJ
Department of Molecular and Cellular Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Hanel
Walter
W
Gaffen
Sarah L
SL
Lin
Xin
X
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D001704:Biopolymers / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D053468:CARD Signaling Adaptor Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D051017:Apoptosis Regulatory Proteins; D001704:Biopolymers; D053468:CARD Signaling Adaptor Proteins; C496467:Card11 protein, mouse; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell