4j2x | pdb_00004j2x
CSL (RBP-Jk) with corepressor KyoT2 bound to DNA
Structural highlights
Function[SUH_MOUSE] Transcriptional regulator that plays a central role in Notch signaling, a signaling pathway involved in cell-cell communication that regulates a broad spectrum of cell-fate determinations. Acts as a transcriptional repressor when it is not associated with Notch proteins. When associated with some NICD product of Notch proteins (Notch intracellular domain), it acts as a transcriptional activator that activates transcription of Notch target genes. Probably represses or activates transcription via the recruitment of chromatin remodeling complexes containing histone deacetylase or histone acetylase proteins, respectively. Specifically binds to the immunoglobulin kappa-type J segment recombination signal sequence. Binds specifically to methylated DNA.[1] [FHL1_MOUSE] May have an involvement in muscle development or hypertrophy. Isoform 2 binds to RBP-J and plays a negative regulatory role in the RBP-J-mediated transcription in mammalian systems. Publication Abstract from PubMedNotch refers to a highly conserved cell-to-cell signaling pathway with essential roles in embryonic development and tissue maintenance. Dysfunctional signaling causes human disease, highlighting the importance of pathway regulation. Notch signaling ultimately results in the activation of target genes, which is regulated by the nuclear effector CSL (CBF-1/RBP-J, Su(H), Lag-1). CSL dually functions as an activator and a repressor of transcription through differential interactions with coactivator or corepressor proteins, respectively. Although the structures of CSL-coactivator complexes have been determined, the structures of CSL-corepressor complexes are unknown. Here, using a combination of structural, biophysical, and cellular approaches, we characterize the structure and function of CSL in complex with the corepressor KyoT2. Collectively, our studies provide molecular insights into how KyoT2 binds CSL with high affinity and competes with coactivators, such as Notch, for binding CSL. These studies are important for understanding how CSL functions as both an activator and a repressor of transcription of Notch target genes. Structure and Function of the CSL-KyoT2 Corepressor Complex: A Negative Regulator of Notch Signaling.,Collins KJ, Yuan Z, Kovall RA Structure. 2014 Jan 7;22(1):70-81. doi: 10.1016/j.str.2013.10.010. Epub 2013 Nov , 27. PMID:24290140[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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