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発表内容

Title:
How to read ubiquitin signals

Shuya Fukai
Laboratory of Structural Biology
Life Science Division
Synchrotron Radiation Research Organization and Institute of Molecular and Cellular Biosciences
The University of Tokyo

Abstract:
Ubiquitin (Ub) is a highly conserved 76-residue protein that can be covalently attached to substrate proteins to regulate a wide variety of biological processes. The terminal carboxylate of Ub is typically attached to the side-chain amino group of substrate lysine residues. Ub itself can be linked to another Ub through its own lysine and N-terminal methionine residues to form Ub chains. Ub has seven lysine residues ( K6 , K11 , K27 , K29 , K33 , K48 and K63 ) and one terminal methionine residue (M1). Therefore, eight different types of Ub chains are produced and transmit different signals to control specific cellular processes. For instance, Ub chains for a signal of the proteasomal degradation are linked through K48, whereas K63- and M1-linked chains play important roles in proteasome-independent processes such as receptor down-regulation, inflammatory signaling and DNA damage response. We have investigated how Ub-chain signals are recognized by Ub receptors and deubiquitinating enzymes in specific signaling contexts. In this seminar, mechanisms for reading the Ub signals will be presented.

References:
Sato, Y., Fujita, H., Yoshikawa, A., Yamashita, M., Yamagata, A., Kaiser, S. E., Iwai, K., Fukai, S. “Specific recognition of linear ubiquitin chains by the Npl4 zinc finger (NZF) domain of the HOIL-1L subunit of the linear ubiquitin chain assembly complex.” Proc. Natl. Acad. Sci. U. S. A. , 108, 20520-20525, 2011

Sato, Y., Yoshikawa, A., Yamashita, M., Yamagata, A., Fukai, S. “Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by NZF domains of TAB2 and TAB3”, EMBO J. , 28, 3903-3909, 2009

Sato, Y., Yoshikawa, A., Mimura, H., Yamashita, M., Yamagata, A., Fukai, S. “Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by tandem UIMs of RAP80.”, EMBO J. , 28, 2461-2468, 2009

Sato, Y., Yoshikawa, A., Yamagata , A., Mimura, H., Yamashita, M., Ookata, K., Nureki, O., Iwai, K., Komada, M., Fukai, S. “Structural basis for specific cleavage of Lys 63-linked polyubiquitin chains.”, Nature , 455, 358-362, 2008