Aberrant regulation of FBW7 in cancer

// Lixia Wang 1,* , Xiantao Ye 1,* , Yueyong Liu 2 , Wenyi Wei 2 , Zhiwei Wang 1 , 1 The Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University, Suzhou, China 2 Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, MA, USA * These authors contributed equally to this work Correspondence: Wenyi Wei, email: // Zhiwei Wang, email: // Keywords :cancer, tumor suppressor, FBW7, SCF, ubiquitination, oncoprotein Received : March 13, 2014 Accepted : March 24, 2014 Published : March 25, 2014 Abstract FBW7 (F-box and WD repeat domain-containing 7) or Fbxw7 is a tumor suppressor, which promotes the ubiquitination and subsequent degradation of numerous oncoproteins including Mcl-1, Cyclin E, Notch, c- Jun, and c-Myc. In turn, FBW7 is regulated by multiple upstream factors including p53, C/EBP-δ, EBP2, Pin1, Hes-5 and Numb4 as well as by microRNAs such as miR-223, miR-27a, miR-25, and miR-129-5p. Given that the Fbw7 tumor suppressor is frequently inactivated or deleted in various human cancers, targeting FBW7 regulators is a promising anti-cancer therapeutic strategy.