English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Importance of class II transactivator leucine-rich repeats for dominant-negative function and nucleo-cytoplasmic transport

MPS-Authors
/persons/resource/persons191007

Camacho-Carvajal,  Margarita M.
Research Group and Chair of Molecular Immunology of the University of Freiburg, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191155

Klingler,  Sebastian
Spemann Laboratory, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191308

Schnappauf,  Felix
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191085

Hake,  Sandra B.
Spemann Laboratory, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191331

Steimle,  Viktor
Spemann Laboratory, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

External Resource
No external resources are shared
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Camacho-Carvajal, M. M., Klingler, S., Schnappauf, F., Hake, S. B., & Steimle, V. (2004). Importance of class II transactivator leucine-rich repeats for dominant-negative function and nucleo-cytoplasmic transport. International Immunology, 16(1), 65-75.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002B-9457-1
Abstract
Class II transactivator (CIITA), the master regulator of MHC class II (MHC-II) gene transcription, shows a complex behavior in terms of self-association, nucleo-cytoplasmic transport and MHC-II gene transactivation. Here, we analyzed the mechanisms of dominant-negative function and nucleo-cytoplasmic transport of CIITA with emphasis on the role of the C-terminal leucine-rich-repeat (LRR) region in these processes. First, we determined nucleo-cytoplasmic transport of endogenous CIITA and thus validated results obtained with epitope-tagged CIITA constructs. LRR mutations in potential protein-protein contact positions lead to either completely blocked or reduced nuclear import, but can also give rise to increased nuclear export. Surprisingly, N-terminally truncated CIITA mutants show dominant-negative inhibition of wild-type CIITA, whether they are located in the nucleus or in the cytoplasm. Integrity of the LRR is necessary for the dominant-negative function of both types of mutants. LRR mutations are dominant over the effect of an exogenously added N-terminal nuclear localization signal (NLS) leading to cytoplasmic localization. Taken together, our results show that the LRR regulate the function of one or several NLS within CIITA, and control both nuclear import and export. Self-association is not affected in these mutants; we therefore suggest that interaction of the LRR with an unknown protein partner may be necessary for import and transactivation function of CIITA.