Graphical Abstracts Current Cancer Drug Targets, 2016, Vol. 16, No. 2 i Graphical AbstractV Current Cancer Drug Targets, 2016, Vol. 16, No. 2 101 Functional Link between BRCA1 and BAP1 through Histone H2A, Heterochromatin and DNA Damage Response Takayo Fukuda, Tomoko Tsuruga, Takako Kuroda, Hiroyuki Nishikawa and Tomohiko Ohta* *Department of Translational Oncology, Institute of Advanced Medical Science, St. Marianna University Graduate School of Medicine, Kawasaki, 216-8511, Japan PRC1 BRCA1/BARD1 RING RING RNF2/BMI1 BRCA1/BARD1 CBX CBX2, 4, 6, 7, 8 CBX1, 3, 5 me H2A C-terminus me H3K27 H3K9 ASXL1 PR-DUB BAP1 Current Cancer Drug Targets, 2016, Vol. 16, No. 2 110 Regulation of Epithelial-Mesenchymal Transition by E3 Ubiquitin Ligases and Deubiquitinase in Cancer Yasumichi Inoue*, Yuka Itoh, Koichi Sato, Fumihiro Kawasaki, Chihiro Sumita, Takahito Tanaka, Daisuke Morishita and Hidetoshi Hayashi* *Department of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe- dori, Mizuho-ku, Nagoya 467-8603, Japan Current Cancer Drug Targets, 2016, Vol. 16, No. 2 119 The SCF-type E3 Ubiquitin Ligases as Cancer Targets Kyoko Kitagawa and Masatoshi Kitagawa* *Department of Molecular Biology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan E1 E2 Ub 㻌 Ub Rbx1 Ub Cul1 Ub Ub Skp1 Substrate F-box protein F-box SCF-type E3 ligase defect stabilization in cancer in cancer oncogenic Fbw7 proteins c-myc, Notch, c-Jun, Cyc E etc overexpression destabilization in cancer in cancer anti-oncogenic Skp2 proteins p27, p21, p57, p130 etc ii Current Cancer Drug Targets, 2016, Vol. 16, No. 2 Graphical Abstracts Current Cancer Drug Targets, 2016, Vol. 16, No. 2 130 E3 Ubiquitin Ligases as Molecular Targets in Human Oral Cancers Kazuma Masumoto* and Masatoshi Kitagawa *Department of Oral and Maxillofacial Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan Oncogenic E3s Tumor suppressive substrates Tumor suppressive E3s Oncogenic substrates Oral carcinogenesis Current Cancer Drug Targets, 2016, Vol. 16, No. 2 136 Protein Knockdown Technology: Application of Ubiquitin Ligase to Cancer Therapy Nobumichi Ohoka, Norihito Shibata, Takayuki Hattori and Mikihiko Naito* *Division of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan Ubiquitylation E2 Proteasomal degradation of target proteins Target Protein Ubiquitin Ligase Ligand for Ligand for Target Protein Ubiquitin Ligase Hybrid Molecule (SNIPER and PROTAC) Current Cancer Drug Targets, 2016, Vol. 16, No. 2 147 Tribbles-Related Protein Family Members as Regulators or Substrates of the Ubiquitin- Proteasome System in Cancer Development Satoshi Sakai*, Chiharu Miyajima, Chiharu Uchida, Yuka Itoh, Hidetoshi Hayashi and Yasumichi Inoue *Department of Molecular Biology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3125, Japan MAPK activation, Wnt signal, hypoxia, ER stress, Dysregulation of E3 ligases etc. E3 ubiquitin ligase Ub Ub TRBs Ub Ub substrate substrate (C/EBPD etc) TRBs cancer progresssion Graphical Abstracts Current Cancer Drug Targets, 2016, Vol. 16, No. 2 iii Current Cancer Drug Targets, 2016, Vol. 16, No. 2 157 RING-, HECT-, and RBR-type E3 Ubiquitin Ligases: Involvement in Human Cancer Chiharu Uchida* and Masatoshi Kitagawa *Research Equipment Center, Hamamatsu University School of Medicine, Hamamatsu, Japan Normal cell function Ub Ub Ub E2 E2 E2 Ub Ub RING E3 HECT E3 RBR E3 Ub Ub Ub substrate substrate substrate Deregulated ubiquitylation E3-substrate binding inhibitors Aberrant function E3 activity inhibitors Cancer Current Cancer Drug Targets, 2016, Vol. 16, No. 2 175 Old Tyrosine Kinase Inhibitors and Newcomers in Gastrointestinal Cancer Treatment Erika Giordani, Federica Zoratto, Martina Strudel, Anselmo Papa*, Luigi Rossi, Marina Minozzi, Davide Caruso, Eleonora Zaccarelli, Monica Verrico and Silverio Tomao *Department of Medico-Surgical Sciences and Biotechnologies, “Sapienza” University of Rome; Oncology Unit, ICOT, Via Faggiana 1668, 04100 Latina, Italy Current Cancer Drug Targets, 2016, Vol. 16, No. 2 186 Non Steroidal Anti Inflammatory Drugs As Gatekeepers Of Colon Carcinoma Highlight New Scenarios Beyond Cyclooxygenases Inhibition Tiziana Guarnieri* *Dept. of Biology, Geology and Environmental Sciences, School of Sciences, Alma Mater Studiorum Università di Bologna, Italy; Center for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi University Hospital, Bologna, Italy; Biostructures and Biosystems National Institute (I.N.B.B.) Interuniversity Consortium, Rome, Italy .