Disease relevance of C21orf33

• Finally, exogenously expressed skeletrophin, but not its RING mutant, increased transcription of Hes1 gene, a downstream effector of Notch pathway in melanoma cells [1].
• These findings establish that HES-1 inhibits both estrogen- and heregulin-beta1-stimulated growth of breast cancer cells, and further suggest that growth inhibition induced in these cells by all-trans retinoic acid occurs via HES-1-mediated downregulation of E2F-1 expression [2].
• Isolation and characterization of GT335, a novel human gene conserved in Escherichia coli and mapping to 21q22.3 [3].
• Rbm15 inhibits Notch-induced HES1 transcription in nonhematopoietic cells but stimulates this activity in hematopoietic cell lines, including 32DWT18 and human erythroleukemia cells [4].
• Early (ES1) and late (ES2) exteroceptive suppression periods elicited by electrical stimulation of the labial commissure during teeth-clenching were recorded over the temporalis muscle in 45 headache patients (25 tension headaches and 20 migraines) and 22 controls [5].

Psychiatry related information on C21orf33

• Brainstem and spinal pathways of untreated patients with idiopathic restless legs syndrome (RLS) were examined using magnetic resonance imaging (MRI), blink reflex, first and second exteroceptive suppression (ES1, ES2) of temporalis muscle, and H reflex [6].

High impact information on C21orf33

• Conditional deletion of Rbp-J, which encodes the major mediator of the Notch pathway, leads to premature differentiation of progenitor cells, a phenotype recapitulated by loss of the basic helix-loop-helix (bHLH) factor Hes1, as well as a conversion of the late (Pit1) lineage into the early (corticotrope) lineage [7].
• To investigate a possible relationship between the exceptional stability of centriole microtubules and the compartmentalization of glutamylated isoforms, we loaded HeLa cells with the monoclonal antibody GT335, which specifically reacts with polyglutamylated tubulin [8].
• We also show that Hes1, a known effector of Notch signaling, potentiates Runx1-mediated transactivation [9].
• In turn, leukemic cells growing in direct contact with bone marrow stromal elements induce activation of Akt, ERK1/2, and STAT3 signaling in MSC, accompanied by significant increase in Hes1 and Bcl-2 proteins, which were all suppressed by QLT0267 and LY294002 [10].
• Based on these observations, we hypothesized that ES1 antigens participate in the formation of cardiac mesenchyme [11].

Chemical compound and disease context of C21orf33

• While sumatriptan caused a significant increase in ES1 duration (p < or = 0.05) both during the migraine interval and during the migraine attack, placebo showed no significant effect on ES1 duration [12].

Biological context of C21orf33

• HES-1 inhibits 17beta-estradiol and heregulin-beta1-mediated upregulation of E2F-1 [2].
• GT335 spans an estimated 13 kb of genomic DNA and is split into seven exons [3].
• The KNP-I gene was mapped between D21S1460 and D21S25 on human chromosome 21q22.3, 26 kb distal to a Not 1 site of D21S1460 [13].
• We have isolated cDNA clones for a novel human protein KNP-I from fetal brain and bone marrow cDNA libraries [13].
• Isolation of cDNA for a novel human protein KNP-I that is homologous to the E. coli SCRP-27A protein from the autoimmune polyglandular disease type I (APECED) region of chromosome 21q22.3 [13].

Anatomical context of C21orf33

• Based on the assumption that structural similarities reflect functional relationship, it may be speculated that ES1 is serving a basic function in mitochondria [14].
• Polyclonal antibodies (ES1) generated against the EDTA-extractable proteins both localized to the cardiac extracellular matrix preceding the transformation of endothelium and blocked this process in culture [11].
• GT335, a monoclonal antibody directed against glutamylated tubulins, stained the centriole/basal bodies and the axonemes of ciliated cells, and the centrioles of non-ciliated cells [15].
• B3 and GT335 were also capable of inhibiting the motility of flagella of Oxyrrhis marina, a 400,000,000 year old species of dinoflagellate, and those of human sperm models [16].
• Localization of the antigens recognized by B3 and GT335 by immunofluorescence techniques revealed their presence along the whole axoneme of sea urchin spermatozoa and flagella of O. marina, except for the distal tip and the cortical microtubule network of the dinoflagellate [16].

Associations of C21orf33 with chemical compounds

• Furthermore, proliferation caused by heregulin-beta1 treatment of T47D cells was inhibited by all-trans retinoic acid and this effect was mediated by HES-1 [2].
• The ES1-positive MBM particulates were removed by extraction with EDTA, but not with PBS, indicating a divalent cation-mediated association of the constituent proteins [17].
• Isotonic saline did not influence the ES1 or ES2 [18].
• First ES1 and ES2 were measured (stimulus intensity 20 mA, stimulus duration 0.2 ms, stimulation frequency 2 Hz, averaging of 10 responses), then the medication was given on a double-blind basis with an autoinjector using either 6 mg sumatriptan or a placebo solution [12].
• The treatments investigated were twice-daily application of aminophylline cream and twice-weekly treatment with Endermologie ES1 [19].

Regulatory relationships of C21orf33

• Interestingly, heregulin-beta1-mediated upregulation of E2F-1 expression was directly inhibited by HES-1 through the same CACGAG-site as seen with estrogen-stimulated induction [2].

Other interactions of C21orf33

• Thus, this novel KNP-I gene could be a candidate gene for autoimmune polyglandular disease type I (APECED) and other disorders mapped to this region [13].
• Database searches revealed that the second gene of this operon, named iaaC, is well conserved evolutionarily and that the encoded protein is homologous to the Escherichia coli protein SCRP-27A, the zebrafish protein ES1, and the human protein KNP-I/GT335 (HES1), all of unknown function and belonging to the DJ-1/PfpI superfamily [20].
• RESULTS: Using HeLa cells stably expressing centrin-green fluorescent protein as a centriole marker, we monitored the effect of microinjecting an anti-(polyglutamylated tubulin) monoclonal antibody, GT335, in G1/S or G2 cells [21].

Analytical, diagnostic and therapeutic context of C21orf33

• Northern blot analysis indicated that the KNP-I gene is ubiquitously expressed in various human tissues [13].
• Using RT-PCR, we detected in the anterior pituitary of adult mouse the expression of all four vertebrate Notch receptors, as well as of Hes1, 5, and 6, key downstream targets and effectors of Notch [22].
• Furthermore, western blotting revealed that exogenous TAp73 suppressed endogenous hairy and enhancer of split-1 (HES-1) protein levels and antagonized the increase in HES-1 protein induced by exogenous N1(ICD) expression [23].
• The sample with the mutation expressed the intracellular Notch1 fragment by immunoblotting and HES1 mRNA by reverse transcription-polymerase chain reaction [24].
• Both ES1 and an anti-fibronectin monoclonal antibody (M3H) co-localized in situ to particles within the MBM; however, no ES1 reactivity towards fibronectin could be detected by ELISA or immunoblot analysis [17].

References