Disease relevance of DEAF1

• Altered subcellular localization of suppressin, a novel inhibitor of cell-cycle entry, is an independent prognostic factor in colorectal adenocarcinomas [1].

Psychiatry related information on DEAF1

• The association with major depression, suicide, and panic disorder of a new functional 5-HT1A polymorphism at C(-1019)G that selectively blocks repression of the 5-HT1A autoreceptor by NUDR further suggests a causative role for altered regulation of this receptor in predisposition to mental illness [2].
• Cell-specific regulation by Deaf-1 could underlie region-specific alterations in 5-HT1A receptor expression in different mood disorders [3].

High impact information on DEAF1

• The SAND domain is a conserved sequence motif found in a number of nuclear proteins, including the Sp100 family and NUDR [4].
• Although chromosome 19q could be excluded, evidence for linkage in the ICCA region was found, with a maximum two-point LOD score of 3.32 for markers D16S3131 and SPN [5].

Biological context of DEAF1

• Structural analysis showed that the N-terminal region of PHD2 contains a Myeloid translocation protein 8, Nervy, and DEAF1 (MYND)-type zinc finger domain, whereas the catalytic domain is located in its C-terminal region [6].
• Although primarily nuclear, cytoplasmic localization of DEAF-1 has been observed, and this suggests the presence of a nuclear export signal (NES) [7].
• Suppressin (SPN) is an inhibitor of cell proliferation that was originally identified and purified to homogeneity from bovine pituitaries (LeBoeuf, R. D., Burns, J. N., Bost, K. L., and Blalock, J. E. (1990) J. Biol. Chem. 265, 158-165) [8].
• Deformed epidermal autoregulatory factor-1 (DEAF-1) is a DNA-binding protein required for embryonic development and linked to clinical depression and suicidal behavior in humans [7].
• Sequence analyses showed that the nucleotide and deduced amino acid sequences of SPN are novel and unrelated to any known vertebrate inhibitors of proliferation [8].

Anatomical context of DEAF1

• Reverse transcriptase-polymerase chain reaction and immunohistochemical analyses showed that the SPN mRNA and the SPN protein are expressed in every tissue examined including testis, spleen, skeletal muscle, liver, kidney, heart, and brain suggesting that SPN may be involved in the control of proliferation in a variety of cell types [8].
• RESULTS: Exogenous SPN inhibited the proliferation of the LS180 cell line, which also has a mutation in one allele of the spn gene [1].
• NUDR protein was colocalized with 5-HT1A receptors in serotonergic raphe cells, hippocampal and cortical neurons, and adult brain regions including raphe nuclei, indicating a role in regulating 5-HT1A autoreceptor expression [9].
• Our experiments indicate that assembly of the SG subcomplex is a prerequisite for targeting SPN to the sarcolemma [10].
• BACKGROUND: The fact that solid pseudopapillary neoplasms of the pancreas (SPNP) occur predominantly in young women suggests that genetic and/or gender-specific factors may play a role in the pathogenesis [11].

Associations of DEAF1 with chemical compounds

• Deletion of these adjacent sequences or mutation of the conserved cysteines or histidine in the zinc binding motif not only inhibits protein interaction but also eliminates DNA binding, demonstrating that DEAF-1 protein-protein interaction is required for DNA recognition [7].
• NUDR-dependent repression was also observed when the 5'-UTR of NUDR was placed onto a heterologous thymidine kinase promoter in an analogous 5'-UTR position but not when placed upstream of transcription initiation [12].
• Cell-specific repressor or enhancer activities of Deaf-1 at a serotonin 1A receptor gene polymorphism [3].
• Repressor or enhancer activities of Deaf-1 or Gal4DBD-Deaf-1 were blocked by histone deacetylase inhibitor trichostatin A [3].

Regulatory relationships of DEAF1

• The 5-HT1A receptor gene is repressed by NUDR/DEAF-1 in raphe cells at the C-, but not at the G-allele of the C(-1019)G polymorphism that is associated with major depression and suicide [13].

Other interactions of DEAF1

• Our data indicate that NUDR is a repressor of the 5-HT1A receptor in raphe cells the function of which is abrogated by a promoter polymorphism [9].
• We have recently identified a new suppressor molecule we named suppressin (SPN) that has all the characteristics of a global negative regulator of the immune system [14].

Analytical, diagnostic and therapeutic context of DEAF1

• In 11 S. pneumoniae culture-negative samples from patients not receiving antibiotics, all three tests were negative in eight, PCR was positive in three (in one of which CPS-CIE was also positive), but SPN-blot was negative in all 11 [15].

References