Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The X11/MINT family proteins are adaptor scaffolding proteins involved in formation of multiprotein complexes, and trafficking and metabolism of membrane proteins such as the beta-amyloid precursor protein. We found that a significant portion of X11L and X11L2 are recovered in nuclear fraction of mouse brain homogenates. EGFP-X11s were not detected in the nucleus of N2a neuroblastoma cells; however, administration of leptomycin B (LMB) induced substantial nuclear accumulation of EGFP-X11L and EGFP-X11L2, while EGFP-X11 showed little accumulation. Fluorescence loss in photobleaching (FLIP) analysis indicated that EGFP-X11L2 and EGFP-X11L are shuttled between the cytoplasm and nucleus, the former more effectively than the latter. We identified a nuclear export signal (NES) in the N-terminus of X11L2, mutation of which induces nuclear accumulation of EGFP-X11L2 in the absence of LMB. X11L2 fused to the Gal4 DNA binding domain (DBD) showed transcriptional activity, suggesting that X11L2 could function as a transcriptional activator if tethered near a promoter. Interestingly, attenuation of the nucleo-cytoplasmic shuttling of GAL4-DBD-X11L2 by mutating the NES or attaching the SV40 nuclear localization signal significantly decreased the apparent transcriptional activity. Our observations suggest that X11L2 functions in the nucleus by a mechanism distinct from conventional transactivators.
 ...
PMID:The X11L/X11beta/MINT2 and X11L2/X11gamma/MINT3 scaffold proteins shuttle between the nucleus and cytoplasm. 1820 94

RBP-J/Su(H)/Lag1, the main transcriptional mediator of Notch signaling, binds DNA with the consensus sequence YRTGDGAD. Notch target genes can be controlled by two opposing activities of RBP-J. The interaction of the Notch intracellular domain with RBP-J induces a weak transcriptional activation and requires an additional tissue-specific transcriptional activator such as bHLH proteins or GATA to mediate strong target gene expression. For example, during Drosophila sensory organ precursor (SOP) cell development, proneural bHLH interacts with Da, a Drosophila orthologue of E2A, to form a tissue-specific activator of Su(H), the Drosophila orthologue of RBP-J. This complex and Su(H) act synergistically to promote the epidermal cell fate. In contrast, a complex of Su(H) with Hairless, a Drosophila functional homologue of MINT, has transcriptional repression activity that promotes SOP differentiation to neurons. Recent conditional loss-of-function studies demonstrated that transcriptional networks involving RBP-J, MINT, and E2A are conserved in mammalian cell differentiation, including multiple steps of lymphocyte development, and probably also in neuronal maturation in adult neurogenesis. During neurogenesis, Notch-RBP-J signaling was thought historically to be involved mainly in the maintenance of undifferentiated neural progenitors. However, the identification of a tissue-specific transcriptional activator of RBP-J-Notch has revealed new roles of RBP-J in the promotion of neuronal maturation. Finally, the Notch-independent function of RBP-J was recently discovered and will be reviewed here.
 ...
PMID:Two opposing roles of RBP-J in Notch signaling. 2081 97