Reprogramming of metabolic systems via COP1 in the process of cellular transformation and cancer progression

2016 Fiscal Year Final Research Report

• Project/Area Number: 26440100
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: Kato Noriko 奈良先端科学技術大学院大学, バイオサイエンス研究科, 助教 (10252785)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 細胞がん化 / エネルギー代謝

Outline of Final Research Achievements

COP1 is an E3 ubiquitin ligase that is involved in tumorigenesis and metabolism. We aimed how cancer-initiating cells acquire a specific energy metabolic system essential for their proliferation in the process of cellular transformation by investigating the COP1’s activities linking both tumorigenesis and metabolism.
In this study, we newly identified COP1’s ligase-complexes and substrates for degradation, and depicted a presumable network map associated with COP1 activities. We are analyzing these factors using various cell culture systems and mouse models. In addition, we found that acute myeloid leukemia-associated MLF1 is an inhibitory factor of the ligase activity of the COP1-Trib1 complex. MLF1 directly interacts with COP1 and interferes with the formation of the COP1-Trib1 complex, thereby stabilizing C/EBPα protein and suppressing AML development in mice. Induction and stabilization of MLF1 expression have a potential as a novel strategy for cancer therapy.

Free Research Field

生物学