Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fruitless (fru) locus was originally defined by a male sterile mutation that promotes male-to-male courtship while suppressing male-to-female courtship in Drosophila melanogaster. The fru promoter-1 pre-RNA generates a set of BTB-zinc finger family FruM proteins expressed exclusively in the male neurons, leading to the formation of sexual dimorphisms in neurons via male-specific neuroblast proliferation, male-specific neural survival, male-specific neuritegenesis or male-specific arbor patterning. Such a wide spectrum of phenotypic effects seems to result from chromatin modifications, in which FruBM recruits Bonus, Histone deacetylase 1 (HDAC1) and/or Heterochromatin protein 1a (HP1a) to ~130 target sites. One established FruBM transcriptional target is the axon guidance protein gene robo1. Multiple transcriptional regulator-binding sites are nested around the FruBM-binding site, and mediate sophisticated modulation of the repressor activity of FruBM. FruBM also binds to the Lola-Q transcriptional repressor to protect it from proteasome-dependent degradation in male but not female neurons as FruBM exists only in male neurons, leading to the formation of sexually dimorphic neural structures. These findings shed light on the multilayered network of transcription regulation orchestrated by the master regulator FruBM.
 ...
PMID:The mode of action of Fruitless: Is it an easy matter to switch the sex? 3142 Sep 27

Evolutionarily conserved SCAN (named after SRE-ZBP, CTfin51, AW-1, and Number 18 cDNA)-domain-containing zinc finger transcription factors (ZSCAN) have been found in both mouse and human genomes. Zscan4 is transiently expressed during zygotic genome activation (ZGA) in preimplantation embryos and induced pluripotent stem cell (iPSC) reprogramming. However, little is known about the mechanism of Zscan4 underlying these processes of cell fate control. Here, we show that Zscan4f, a representative of ZSCAN proteins, is able to recruit Tet2 through its SCAN domain. The Zscan4f-Tet2 interaction promotes DNA demethylation and regulates the expression of target genes, particularly those encoding glycolytic enzymes and proteasome subunits. Zscan4f regulates metabolic rewiring, enhances proteasome function, and ultimately promotes iPSC generation. These results identify Zscan4f as an important partner of Tet2 in regulating target genes and promoting iPSC generation and suggest a possible and common mechanism shared by SCAN family transcription factors to recruit ten-eleven translocation (TET) DNA dioxygenases to regulate diverse cellular processes, including reprogramming.
 ...
PMID:The Zscan4-Tet2 Transcription Nexus Regulates Metabolic Rewiring and Enhances Proteostasis to Promote Reprogramming. 3266 44

Interleukin enhancer-binding factor 2 (ILF2) forms a heterodimer with interleukin enhancer-binding factor 3 (ILF3) via double-stranded RNA-binding motif and zinc finger associated domain and thus regulates gene expression and cancer cell growth. However, how ILF2 is degraded in cells remains elusive. In this work, using stable isotope labeling by amino acids in cell culture (SILAC) quantitative proteomics, we find that ILF2 is downregulated in cells expressing cereblon (CRBN). Using affinity purification and immunoblotting analysis, we demonstrate that CRBN interacts with ILF2 and functions as a substrate receptor of the cullin-4 RING E3 ligase complex. Biochemical experiments disclose that CRBN expression reduces ILF2 protein level and this reduction is diminished when the proteasome is inhibited. Upon protein synthesis inhibition, the degradation of ILF2 is enhanced by CRBN. Moreover, CRBN promotes the ubiquitination of ILF2 and thus results in the ubiquitin-mediated proteasomal degradation. Analyses of previously identified post-translational modification sites and the crystal structure of ILF2 discover the potential ubiquitination sites on ILF2. Through mutagenesis and biochemical experiments, we further reveal that the K45R mutation completely abolishes the effect of CRBN on ILF2, suggesting that this is the key residue responsible for its ubiquitination. Taken together, we identify an E3 ligase that regulates ILF2 and uncover a molecular pathway for its degradation. This work might be helpful to elucidate the molecular mechanism by which CRBN regulates diverse cellular functions.
 ...
PMID:Cereblon Promotes the Ubiquitination and Proteasomal Degradation of Interleukin Enhancer-Binding Factor 2. 3300 60


<< Previous 1 2 3 4 5 6