Taka-Aki Sato, PhD

The primary goals of our current and future research are to understand the mechanisms of signal transduction of apoptosis (programmed cell death) in normal and malignant tumor cells and to identify the putative tumor suppressor gene for head and neck tumors. In particular, we have been interested in identifying putative signal transducing molecules that regulate induction of apoptosis or promotion of cell survival by TNF/NGF receptor family.

Recently, we have identified putative signal transducing proteins that associate with the cytoplasmic domains of Fas and CD40 receptors, including a protein tyrosine phosphatase (FAP-1) and a novel TRAF-domain protein (CAP-1), using a yeast two-hybrid approach. We found that the carboxy terminal 3 amino acids of Fas are necessary and sufficient for interaction with the third PDZ domain of FAP-1. Gene-transfer experiments suggested that FAP-1 might somehow inhibit Fas-generated signals that lead to apoptosis. These findings are consistent with an inhibitory effect of FAP-1 on Fas-signal transduction. Further investigations of the physiological function of FAP-1 and CAP-1 in vivo will improve understanding of the signal transduction pathways through which Fas and CD40 controls apoptosis and could contribute to novel therapies for cancer and immune disorders.

Selected Publications:

• Takayama, S., Sato, T., Krajewski, S., Kochel, K., Irie, S., Millan, J., and Reed, J.C. Cloning and functional analysis of BAG-1 A novel Bcl-2 binding protein with anti-cell death activity. Cell. 80: 279-284 (1995).

• Sato, T., Irie, S., and Reed, J.C. A novel member of the TRAF family of putative signal transducing proteins binds to the cytosolic domain of CD40. FEBS Letter 358: 113-118 (1995).

• Sato, T., Irie, S., Kitada, S., and Reed, J.C. FAP-1: a protein tyrosine phosphatase that associates with Fas. Science 268: 411-415 (1995).

• Inazawa, J., Ariyama, T., Abe, T., Druck, T., Ohta, T., Huebner, K., Yanagisawa, J., Reed, J. C., and Sato, T. FAP-1, a Fas-associated protein tyrosine phosphatase, is located on the long arm of chromosome 4 at band q21.3. Genomics 31: 240-242 (1996).

• Sarid, R., Sato, T., Bohenzky, R.A., Russo, J.J., and Chang, Y. Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a functional Bcl-2 homolog. Nature Medicine 3: 293-298 (1997).

• Yanagisawa, J., Takahashi, M., Kanki, H., Yano-Yanagisawa, H., Sawa, E., Nishitoba, T., Tazunoki, T., Kamishohara, M., Kataoka, S., and Sato, T. The molecular interaction of Fas and FAP-1: A tripeptide blocker of human Fas with FAP-1 promotes Fas-induced apoptosis. J. Biol. Chem. 272: 8539-8545 (1997).

[Go to top of Document]