Self-association of class II transactivator correlates with its intracellular localization and transactivation.
Class II transactivator (CIITA) is the master regulator of major histocompatibility complex class II genes that regulates both B lymphocyte-specific and interferon gamma-inducible expression. Here we identify protein regions and examine mechanisms that determine the intracellular distribution of CIITA. We show that two separate regions of CIITA mediate nuclear export: amino acids 1-114 and 408-550. Both regions interact with the export receptor CRM-1. The CIITA region spanning amino acids 408-550 of CIITA also determines its ability for homotypic self-association as well as heterotypic interactions with other regions residing at the amino and carboxyl termini of the protein. These observations are in line with data demonstrating that co-expression of amino- and carboxyl-terminal parts of CIITA promote subcellular relocalization and, remarkably, rescue transcriptional activation by individually inert molecules. CIITA point mutations that impair nuclear import and abolish its activation function show reduced self-association. We propose that the concerted action of homo- and heterotypic interactions of CIITA determine proper protein configuration that in turn controls its nucleocytoplasmic trafficking.
Kretsovali
A
A
Foundation for Research and Technology, Institute of Molecular Biology and Biotechnology, Heraklion, 711 10 Crete, Greece. papamath@imbb.forth.gr
Spilianakis
C
C
Dimakopoulos
A
A
Makatounakis
T
T
Papamatheakis
J
J
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D017931:DNA Primers; D005816:Genetic Complementation Test; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D009687:Nuclear Proteins; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
D017931:DNA Primers; D008164:Luminescent Proteins; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D049452:Green Fluorescent Proteins