Address
Room: LTC 12732
987696 Nebraska Medical Center
University of Nebraska Medical Center
Omaha, NE 68198-7696

Nebraska Center for Cellular Signaling

Telephone: (402) 559-4639
Fax: (402) 559-3739
Email: mfurukawa@unmc.edu  

Education:

• M.D., Ph.D., Kyushu University, Japan

• Protein ubiquitination regulates numerous cellular functions through proteasome dependent proteolysis and other pathways. The specificity of the ubiquitination is conferred by an E3 ubiquitin ligase that interacts with both a ubiquitin conjugatinig enzyme and a specific substrate to ligate a ubiquitin to the substrate. In this aspect, E3 ubiquitin ligases are the key components for regulating numerous cellular functions through ubiquitin-signaling pathways. The cullin family ubiquitin ligases are evolutionarily conserved multi-subunit E3 ubiquitin ligases that consist of three modules, a cullin family protein as a scaffold, a small ring finger protein as a catalytic subunit, and receptor molecules for targeting a specific substrate. An evolutionarily conserved modular feature of cullin ubiquitin ligases and the recent studies of a limited number of cullin ubiquitin ligases suggest that the cullin famly of E3 ligases targets a large number of substrates to control numerous cellular functions. Misregulation of cullin ligases is also linked to human diseases including cancers. However, many of their substrates and regulatory mechanisms are still not known. Our long-term research goal is to understand functions and regulations of cullin family ligases that will help us to figure out the cellular regulatory mechanisms which are related to human diseases and cancers controlled by the ubiquitin-signaling pathway. Recently, we have identified BTB domain containing proteins as substrate receptor molecules for CUL3-ROC1 E3 ligases and proposed the BTB-CUL3-ROC1 E3 ligase model. In this model, the CUL3 ligase complex could target a large number of substrates for ubiquitination through more than 200 BTB domain containing proteins in human cells. Many of those BTB proteins have been linked to important cellular functions and human diseases. Our current work focuses on substrates, functions and regulations of individual BTB-CUL3-ROC1 E3 ligases using genetic, biochemical and proteomic approaches.

• National Institutes of Health, Nebraska Center for Cellular Signaling (PI: Wheelock, MJ). Project “The function of BTB-CUL3 ligaes in mitosis”, Project reader: Manabu Furukawa; 07/01/06 to 09/30/08.

• Furukawa, M., Andrews, P. S. & Xiong, Y. Assays for RING family ubiquitin ligases. Methods Mol Biol 301, 37-46 (2005).
• Furukawa, M. & Xiong, Y. BTB protein Keap1 targets antioxidant transcription factor Nrf2 for ubiquitination by the Cullin 3-Roc1 ligase. Mol Cell Biol 25, 162-71 (2005).
• Furukawa, M., He, Y. J., Borchers, C. & Xiong, Y. Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases. Nat Cell Biol 5, 1001-7 (2003).
• Liu, J., Furukawa, M., Matsumoto, T. & Xiong, Y. NEDD8 modification of CUL1 dissociates p120(CAND1), an inhibitor of CUL1-SKP1 binding and SCF ligases. Mol Cell 10, 1511-8 (2002).
• Furukawa, M., Ohta, T. & Xiong, Y. Activation of UBC5 ubiquitin-conjugating enzyme by the RING finger of ROC1 and assembly of active ubiquitin ligases by all cullins. J Biol Chem 277, 15758-65 (2002).
• Furukawa, M., Zhang, Y., McCarville, J., Ohta, T. & Xiong, Y. The CUL1 C-terminal sequence and ROC1 are required for efficient nuclear accumulation, NEDD8 modification, and ubiquitin ligase activity of CUL1. Mol Cell Biol 20, 8185-97 (2000).