Reactome: A Curated Pathway Database

Regulation of expression of SLITs and ROBOs

Stable Identifier
Homo sapiens
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Expression of SLIT and ROBO proteins is regulated at the level of transcription, translation and protein localization and stability. LIM-homeodomain transcription factors LHX2, LHX3, LHX4, LHX9 and ISL1 have so far been implicated in a cell type-dependent transcriptional regulation of ROBO1, ROBO2, ROBO3 and SLIT2 (Wilson et al. 2008, Marcos-Mondejar et al. 2012, Kim et al. 2016). Homeobox transcription factor HOXA2 is involved in transcriptional regulation of ROBO2 (Geisen et al. 2008). Transcription of SLIT1 during optic tract development in Xenopus is stimulated by FGF signaling and may also involve the transcription factor HOXA2, but the mechanism has not been established (Atkinson-Leadbeater et al. 2010). PAX6 and the homeodomain transcription factor NKX2.2 are also implicated in regulation of SLIT1 transcription (Genethliou et al. 2009). An RNA binding protein, MSI1, binds ROBO3 mRNA and promotes its translation, thus increasing ROBO3 protein levels (Kuwako et al. 2010). A poorly studied E3 ubiquitin ligase ZSWIM8 promotes degradation of ROBO3 (Wang et al. 2013). ROBO1 is protein half-life is increased via deubiquitination of ROBO1 by a ubiquitin protease USP33 (Yuasa-Kawada et al. 2009, Huang et al. 2015). Interaction of SLIT2 with DAG1 (dystroglycan) is important for proper localization of SLIT2 at the floor plate (Wright et al. 2012). Interaction of SLIT1 with a type IV collagen COL4A5 is important for localization of SLIT1 to the basement membrane of the optical tectum (Xiao et al. 2011).

Literature References
PubMed ID Title Journal Year
22457488 The lhx2 transcription factor controls thalamocortical axonal guidance by specific regulation of robo1 and robo2 receptors J. Neurosci. 2012
19258013 Spatially distinct functions of PAX6 and NKX2.2 during gliogenesis in the ventral spinal cord Biochem. Biophys. Res. Commun. 2009
20696379 Neural RNA-binding protein Musashi1 controls midline crossing of precerebellar neurons through posttranscriptional regulation of Robo3/Rig-1 expression Neuron 2010
20071533 Dynamic expression of axon guidance cues required for optic tract development is controlled by fibroblast growth factor signaling J. Neurosci. 2010
24012004 The EBAX-type Cullin-RING E3 ligase and Hsp90 guard the protein quality of the SAX-3/Robo receptor in developing neurons Neuron 2013
27819291 ISL1-based LIM complexes control Slit2 transcription in developing cranial motor neurons Sci Rep 2016
21729787 Assembly of lamina-specific neuronal connections by slit bound to type IV collagen Cell 2011
25242263 USP33 mediates Slit-Robo signaling in inhibiting colorectal cancer cell migration Int. J. Cancer 2015
18701067 A molecular program for contralateral trajectory: Rig-1 control by LIM homeodomain transcription factors Neuron 2008
18547144 Hox paralog group 2 genes control the migration of mouse pontine neurons through slit-robo signaling PLoS Biol. 2008
23217742 Dystroglycan organizes axon guidance cue localization and axonal pathfinding Neuron 2012
19706539 Deubiquitinating enzyme USP33/VDU1 is required for Slit signaling in inhibiting breast cancer cell migration Proc. Natl. Acad. Sci. U.S.A. 2009
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Orthologous Events