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| Status |
Public on Mar 24, 2009 |
| Title |
TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by SNP array
SNP genotyping by SNP array
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| Summary |
Classical Hodgkin lymphoma (cHL) is one of the most common malignant lymphomas. It is characterized by the presence of rare Hodgkin and Reed/Sternberg (HRS) cells embedded in an extensive inflammatory infiltrate. Constitutive activation of nuclear factor-kappaB (NF-kappaB) in HRS cells which transcriptionally regulates expression of multiple anti-apoptotic factors and pro-inflammatory cytokines plays a central role in the pathogenesis of cHL (1, 2). In non-stimulated condition, NF-kappaB proteins are rendered inactive by binding to their inhibitors (IkappaB s), which sequester them in the cytoplasm. Stimulation of multiple receptors activates the IkappaB kinase (IKK) complex that phosphorylates IkappaB at two specific serine residues, followed by its ubiquitination and proteasomal degradation, thereby releasing NF-kappaB proteins and allowing their nuclear translocation (3). Recently, two studies provided further insights into the molecular mechanisms of IKK activation upon TNF stimulation (4, 5). Activation of the IKK complex and subsequent NF-kappaB activation requires Lys63 polyubiquitination of RIP1, a kinase which is recruited to the receptor upon TNF stimulation. IKK-gamma (NEMO), the regulatory subunit of the IKK complex, specifically recognizes these Lys63-linked polyubiquitins attached to RIP1 and thereby activates IKK and NF-kappaB (4, 5). A20 is an ubiquitin-modifying enzyme that inhibits NF-kappaB activation in succession of tumor necrosis factor (TNF) receptor and Toll-like receptor induced signals (6-8). This enzyme removes Lys63 linked ubiquitin chains from RIP1 and adds Lys48 polyubiquitins to RIP1, thereby targeting this factor for proteasomal degradation, thus explaining the molecular mechanism of NF-kappaB inhibition by A20 (6). A20 likely inhibits NF-kappaB acitivity also by additional means, including interaction with TRAF1 and TRAF2 (9).
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| Overall design |
SNP 6.0 array (Affymetrix) analyses were performed according to the manufacturer's directions on DNA extracted from three Hodgkin cell lines (L1236, HDLM-2, U-HO1), HapMap samples included in the Genotyping Console Software 3.0 were used as references.
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| Contributor(s) |
Schmitz R, Hansmann M, Bohle V, Martin-Subero JI, Hartmann S, Mechtersheimer G, Klapper W, Vater I, Giefing M, Gesk S, Stanelle J, Siebert R, Küppers R |
| Citation(s) |
19380639 |
| Submission date |
Mar 17, 2009 |
| Last update date |
Nov 27, 2018 |
| Contact name |
Inga Vater |
| E-mail(s) |
ivater@medgen.uni-kiel.de
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| Phone |
00494315973549
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| Fax |
00494315971880
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| Organization name |
Univeesity hospital Schleswig-Holstein
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| Department |
Institute of Human Genetics
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| Street address |
Arnold-Heller-Strasse 3, Haus 10
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| City |
Kiel |
| ZIP/Postal code |
24105 |
| Country |
Germany |
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| Platforms (1) |
| GPL6801 |
[GenomeWideSNP_6] Affymetrix Genome-Wide Human SNP 6.0 Array |
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| Samples (3) |
| GSM381297 |
D08-62 Hodgkin cell line L1236 SNP 6.0 array |
| GSM381298 |
D08-864 Hodgkin cell line HDLM2 SNP 6.0 array |
| GSM381299 |
D08-1255 Hodgkin cell line U-HO1 SNP 6.0 array |
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| Relations |
| BioProject |
PRJNA116491 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE15264_RAW.tar |
232.0 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data provided as supplementary file |
| Processed data included within Sample table |
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