| Co-Investigator(Kenkyū-buntansha) |
KITAURA Hirotake Hokkaido Univ., Grad. School of Pharm. Sci., Res. Associate, 大学院・薬学研究科, 助手 (10281817)
TAIRA Takahiro Hokkaido Univ., Grad. School of Pharm. Sci., Asso. Prof., 大学院・薬学研究科, 助教授 (70197036)
ARIGA Sanae Hokkaido Univ., Grad. School of Pharm. Sci., Prof., 医療技術短期大学部, 教授 (90184283)
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| Research Abstract |
We have identified several c-Myc binding proteins whose functions would modify or regulate the versatile functions of c-Myc. Proteins we identified are AMY-1, MM-1, MSSP, CBF/NF-Y, ORC1, CDC6 and cdk inhibitor p21. AMY-1, MM-1 and MSSP are novel proteins and their cDNAS were cloned. These proteins were classified to the categories including factors for transcription (AMY-1, MM-1 and CBF/NF-Y), DNA replication (MSSP, ORC1 and CDC6) and cell-cycle movement (p21). In terms of transcription function of c-Myc, AMY-1 acted as a positive factor and the others were as negative factors. Especially MM-1 has a character for a putative tumor suppresser; the substitution of amino acid from alanine to arginine at a position of 157 of MM-1 was quite frequently occurred in cells derived from both cultured cells and cancer patient tissues of lymphoma, leukemia and tong cancer. This arginine mutation abrogated the negative effects of MM-1 on c-Myc.
In addition to c-Myc-related function of AMY-1, AMY-1 was found to contain the dynamic function affecting A-kinase and actin polymerization. AMY-1 bound to AKAP84 and its alternative splicing variant, AKAP149, both of which anchored A-kinase to the respective cell location. After AMY-1 bound to AKAP84, A-kinase complex turned to move on the surface of mitochondria of sperm and worked for sperm mobilization. AMY-1 bound to AKAP149 made the actin be polymerized on the mitochondria around nucle. These structural different organization of actin filaments may tend to the tumor formation.
Null-mutation of MSSP tended to be lethal during developmental stage. These finding altogether suggest that c-Myc binding proteins play roles at crucial steps of cell maturation, fertilization in addition to the modulation to c-Myc functions.
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