Since then, ribosomal components have been widely observed as eff

Since then, ribosomal components have been widely observed as effectors of Notch. The selleck chemicals Temsirolimus Notch transcription reporter measurements compliment these long standing, yet mechanistically unknown, genetic interactions. One mechanism proposed to explain the relatively specific genetic interactions between Minute mutations and Notch, is the possibility of specific translational effects. For instance, the translation of long transcripts such as the one encoding Notch itself may be sensitive to lower levels of specific ribosomal components. In contrast, an alternative hypothesis has been presented that these ribosomal proteins may have post translational effects on key components of Notch signaling. Minute pro tein mutations are not found in the active site of the ribosome, as the peptide synthesis reaction is catalyzed exclusively by RNA in the core, but rather on the sur face of the ribosome.

Current structural and biochemical studies have demonstrated post translational roles for these surface coating ribosomal proteins. This includes the folding of nascent peptide chains either directly on the surface of the ribosome or by the co recruitment of protein chaperones. The protein protein interaction map suggests that these types of post trans lational interactions may be directed towards the core chromatin components of the Notch network. Such a direct mechanism could explain the tran scriptional effects described in this study, as well as the long standing genetic observations between Notch and the Minute class of mutations.

Transcription factors that affect Notch dependent transcription Analysis of the genes identified in the screen revealed a number of transcription factors that affect Notch depen dent transcription. Among these are cnc and maf S that are known to form a strong transcriptional activator complex. RNAi targeting of either of these two genes strongly suppressed both the Notch induced as well as non induced E m3 reporter activity. Also, among the 15 transcription factors that promote Notch activity, we found the DNA binding protein Deaf 1. Cnc, maf S, and Deaf 1 are reported to interact with the Hox protein Deformed to regu late segmentation, but their roles in other developmental events are not known. Our results provide a possi ble role of these proteins in Drosophila development by promoting Notch signaling.

Another transcription factor that we found to play an agonistic role in Notch signaling is the homeobox con taining protein Aristaless. Al has been tentatively linked to Notch signaling, as it cell autono mously represses the Notch ligand Delta in the pretarsus during leg morphogenesis. It is possible that al is involved in a Notch mediated lateral inhibition mechan ism, where al expressing cells remain undifferentiated by favoring active Notch signaling whereas their neighbor ing cells Drug_discovery are free to express Delta and differentiate.

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