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