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Review
. 2010 Sep;67(17):2957-68.
doi: 10.1007/s00018-010-0391-x. Epub 2010 May 11.

Non-canonical activation of Notch signaling/target genes in vertebrates

Rajendran Sanalkumar  1 , Sivadasan Bindu Dhanesh, Jackson James
Affiliations
Review

Non-canonical activation of Notch signaling/target genes in vertebrates

Rajendran Sanalkumar et al. Cell Mol Life Sci. 2010 Sep.

Abstract

Evolutionarily conserved Notch signaling orchestrates diverse physiological mechanisms during metazoan development and homeostasis. Classically, ligand-activated Notch receptors transduce the signaling cascade through the interaction of DNA-bound CBF1-co-repressor complex. However, recent reports have demonstrated execution of a CBF1-independent Notch pathway through signaling cross-talks in various cells/tissues. Here, we have tried to congregate the reports that describe the non-canonical/CBF1-independent Notch signaling and target gene activation in vertebrates with specific emphasis on their functional relevance.

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Figures

Fig. 1
Fig. 1
Schematic of canonical Notch signaling: Canonical Notch signaling is activated by its ligand leading to γ-secretase cleavage of Notch intracellular domain (NICD) which in turn translocates into the nucleus. There, it converts the transcriptional co-repressor complex into an activator complex by recruiting MAML and specific co-activators (Co-A) following displacement of the co-repressor complex (including NCoR, HDAC and Co-R). Subsequently, the specific co-activator complex will trigger the transcription of Notch target genes (Hes/Herp family)
Fig. 2
Fig. 2
Schematic of non-canonical Notch signaling/target gene activation. a The non-canonical Notch signaling (Type-I) pathway requires ligand mediated cleavage of Notch receptor but transduces the signals independent of CBF1 interaction. Here, the cleaved NICD interacts with tissue-specific co-activators (Co-A) and other undefined factors to activate downstream targets/functions. The cleaved NICD can also interact with components of other signaling pathways and activate downstream components of Notch signaling. b Non-canonical Notch target gene activation (Type-II) is completely devoid of either ligand-mediated NICD-release or CBF1-interaction, and hence target genes are activated through alternate signaling mechanisms. Downstream effectors of JNK, Shh and Wnt are known to directly activate the expression of Hes-1/Hairy-1 independent of Notch/CBF1 interaction. c Classification of Notch signaling and its functional implication. References for each signaling pathway are given in square brackets
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