Disease relevance of ONECUT2

• Cell lines generated from metastases of involved lymph nodes (OC2) and ascites (OC1) of patients with esophageal cancer do not display, however, hyperphosphorylation of ERK1/2 [1].
• The purified alpha T3/OC2, alpha OC/TR, and OV-TL3/CD3 were all able to mediate highly specific lysis of various ovarian-carcinoma cell lines [2].
• Activation of p53 signalling in acetylsalicylic acid-induced apoptosis in OC2 human oral cancer cells [3].
• The number of intermenstrual bleeding days was highest for OC3 (p = 0.001) and higher for OC2 when compared with OC1 (p < 0.006) [4].
• OC2 Calcifying epithelial odontogenic tumor of the mandible with clear cell component treated by conservative surgery: report of a case with 30 months of follow-up [5].

High impact information on ONECUT2

• An examination of intestinal expression patterns showed that all three OC factors are expressed at detectable levels in adult mouse duodenum, with OC-2 predominant [6].
• Indeed, electrophoretic mobility shift assays, chromatin immunoprecipitation, and transfection experiments demonstrated that Onecut-2 is able to bind to the granuphilin promoter and to repress its transcriptional activity [7].
• OC-2, a novel mammalian member of the ONECUT class of homeodomain transcription factors whose function in liver partially overlaps with that of hepatocyte nuclear factor-6 [8].
• The amino acid sequence of OC-2 contains several regions of high similarity to HNF-6 [8].
• The recognition properties of OC-2 for binding sites present in regulatory regions of liver-expressed genes differ from, but overlap with, those of HNF-6 [8].

Biological context of ONECUT2

• Like HNF-6, OC-2 stimulates transcription of the hnf-3beta gene in transient transfection experiments, suggesting that OC-2 participates in the network of transcription factors required for liver differentiation and metabolism [8].
• The OC-2 gene is located on human chromosome 18 [8].
• Moreover, we show that silencing of Onecut-2 by RNA interference increases Granuphilin expression and mimics the effect of mir-9 on stimulus-induced exocytosis [7].
• Based on these results, we searched in 56 WS2 patients for mutations in the OC2 gene or in OC-2 binding sites in the MITF promoter, but none was found [9].
• OC2 Seasonality Affects on Sperm Motility Kinematic Parameters of Murciano-Granadina Bucks [10].

Anatomical context of ONECUT2

• We show that mir-9 acts by diminishing the expression of the transcription factor Onecut-2 and, in turn, by increasing the level of Granuphilin/Slp4, a Rab GTPase effector associated with beta-cell secretory granules that exerts a negative control on insulin release [7].
• This cDNA predicts a 329-amino acid preprocathepsin with more than 50% identity to both human cathepsin S and cathepsin L and 94% identity to a rabbit cDNA, termed OC2, recently isolated from osteoclasts [11].
• Based on its high homology to OC2, we have named the human enzyme cathepsin O. Cathepsin O mRNA was identified as a single approximately 1.7 kb transcript in cultures of 15-day-old monocyte-derived macrophages, but was not expressed in human monocytes or alveolar macrophages [11].
• We show here that the cut-homeodomain transcription factor Onecut-2 (OC-2) is expressed in melanocytes and binds to the MITF gene promoter [9].
• Supernatants from primary cultures of human oral mucosal keratinocyte and oral cancer-derived cells (KB and OC2) were analyzed by means of gelatin zymography [12].

Associations of ONECUT2 with chemical compounds

• OC-2 was found to encode a novel cysteine proteinase, tentatively called cathepsin K, which is predominantly expressed in osteoclasts [13].
• STUDY DESIGN: A randomized clinical trial evaluated 192 women on 50 micrograms of ethinyl estradiol and 1.0 mg of norethindrone (OC1), 35 micrograms ethinyl estradiol and 1.0 mg of norethindrone (OC2), and 35 micrograms ethinyl estradiol and 0.5 mg norethindrone (OC3) over nine cycles [4].

Analytical, diagnostic and therapeutic context of ONECUT2

• Using 2,3,5,6-tetrafluorophenyl N-(S-benzoylthioacetyl)glycylglycyl-p-aminobenzoate (OC2) >60% of the (99m)Tc complex was obtained at 80 degrees C in 20 min, which was separated from the free ligand and impurities by HPLC [14].
• In this study, using flow cytometry, we have found that a 24-h berberine treatment up-regulated the multidrug-resistant transporter (pgp-170) expression in two oral (KB, OC2), two gastric (SC-M1, NUGC-3) and two colon (COLO 205, CT 26) cancer cell lines [15].
• METHODS: Seven human oral cancer cell lines KB, SCC4, SCC9, SCC15, SCC25, OEC-M1, OC1 and OC2 were used for cell culture experiments [16].

References