| Gene information | Literature | Expression | lncRNA | Mutation | Homolog |
Basic Information | |
|---|---|
Gene ID | 5015 |
Name | OTX2 |
Synonymous | orthodenticle homeobox 2;OTX2;orthodenticle homeobox 2 |
Definition | homeobox protein OTX2|orthodenticle homolog 2 |
Position | 14q22.3 |
Gene type | protein-coding |
Title | Abstract |
| Identification of OTX2 as a medulloblastoma oncogene whose product can be targeted by all-trans retinoic acid. | Through digital karyotyping of permanent medulloblastoma cell lines, we found that the homeobox gene OTX2 was amplified more than 10-fold in three cell lines. Gene expression analyses showed that OTX2 transcripts were present at high levels in 14 of 15 (93%) medulloblastomas with anaplastic histopathologic features. Knockdown of OTX2 expression by siRNAs inhibited medulloblastoma cell growth in vitro, whereas pharmacologic doses of all-trans retinoic acid repressed OTX2 expression and induced apoptosis only in medulloblastoma cell lines that expressed OTX2. These observations suggest that OTX2 is essential for the pathogenesis of anaplastic medulloblastomas and that these tumors may be amenable to therapy with all-trans-retinoic acid. |
| Microarray discovery of new OGT substrates: the medulloblastoma oncogene OTX2 is O-GlcNAcylated. | O-GlcNAc transferase (OGT) is a serine/threonine glycosyltransferase that is essential for development and continues to be critically important throughout life. Understanding OGT s complex biology requires identifying its substrates. Here we demonstrate the utility of a microarray approach for discovering novel OGT substrates. We also report a rapid method to validate OGT substrates that combines in vitro transcription-translation with O-GlcNAc mass tagging. Among the validated new OGT targets is Orthodenticle homeobox 2 (OTX2), a transcription factor critical for brain development, which is primarily expressed only during early embryogenesis and in medulloblastomas, where it functions as an oncogene. We show that endogenous OTX2 from a medulloblastoma cell line is O-GlcNAcylated at several sites. Our results demonstrate that protein microarray technology, combined with the target validation strategy we report, is useful for identifying biologically important OGT substrates, including substrates not present in most tissue types or cell lines. |