PDCD2
Programmed cell death protein 2 is a protein that in humans is encoded by the PDCD2 gene.[3][4]
Function
This gene encodes a nuclear protein expressed in a variety of tissues. The rat homolog, Rp8, is transiently expressed in immature thymocytes and is thought to be involved in programmed cell death. Expression of the human gene has been shown to be repressed by BCL6, a transcriptional repressor required for lymph node germinal center development, suggesting that BCL6 regulates apoptosis by its effects on PDCD2. This gene is closely linked on chromosome 6 to the gene for TBP, the TATA binding protein. Six transcripts encoding different proteins have been identified.[4]
Interactions
PDCD2 has been shown to interact with Host cell factor C1[5] and Parkin (ligase).[6]
Model organisms
Model organisms have been used in the study of PDCD2 function. A conditional knockout mouse line called Pdcd2tm1b(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[7] Male and female animals underwent a standardized phenotypic screen[8] to determine the effects of deletion.[9][10][11][12] Additional screens performed: - In-depth immunological phenotyping[13]
Pdcd2 knockout mouse phenotype
| Characteristic | Phenotype |
| All data available at.[8][13] |
| Insulin | Normal |
| Homozygous viability at P14 | Abnormal |
| Recessive lethal study | Abnormal |
| Body weight | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Normal |
| Haematology 16 Weeks | Normal |
| Peripheral blood leukocytes 16 Weeks | Normal |
| Heart weight | Normal |
| Cytotoxic T Cell Function | Normal |
| Spleen Immunophenotyping | Normal |
| Mesenteric Lymph Node Immunophenotyping | Normal |
| Bone Marrow Immunophenotyping | Normal |
| Epidermal Immune Composition | Normal |
| Influenza Challenge | Normal |
|
References
- ↑ "Human PubMed Reference:".
- ↑ "Mouse PubMed Reference:".
- ↑ Kawakami T, Furukawa Y, Sudo K, Saito H, Takami S, Takahashi E, Nakamura Y (Aug 1995). "Isolation and mapping of a human gene (PDCD2) that is highly homologous to Rp8, a rat gene associated with programmed cell death". Cytogenetics and Cell Genetics. 71 (1): 41–3. doi:10.1159/000134058. PMID 7606924.
- 1 2 "Entrez Gene: PDCD2 programmed cell death 2".
- ↑ Scarr RB, Sharp PA (Aug 2002). "PDCD2 is a negative regulator of HCF-1 (C1)". Oncogene. 21 (34): 5245–54. doi:10.1038/sj.onc.1205647. PMID 12149646.
- ↑ Fukae J, Sato S, Shiba K, Sato K, Mori H, Sharp PA, Mizuno Y, Hattori N (Feb 2009). "Programmed cell death-2 isoform1 is ubiquitinated by parkin and increased in the substantia nigra of patients with autosomal recessive Parkinson's disease". FEBS Letters. 583 (3): 521–5. doi:10.1016/j.febslet.2008.12.055. PMID 19146857.
- ↑ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
- 1 2 "International Mouse Phenotyping Consortium".
- ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410
. PMID 21677750. - ↑ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- ↑ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
- ↑ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
- 1 2 "Infection and Immunity Immunophenotyping (3i) Consortium".
Further reading
- Baron BW, Anastasi J, Thirman MJ, Furukawa Y, Fears S, Kim DC, Simone F, Birkenbach M, Montag A, Sadhu A, Zeleznik-Le N, McKeithan TW (Mar 2002). "The human programmed cell death-2 (PDCD2) gene is a target of BCL6 repression: implications for a role of BCL6 in the down-regulation of apoptosis". Proceedings of the National Academy of Sciences of the United States of America. 99 (5): 2860–5. doi:10.1073/pnas.042702599. PMC 122438. PMID 11854457.
- Scarr RB, Sharp PA (Aug 2002). "PDCD2 is a negative regulator of HCF-1 (C1)". Oncogene. 21 (34): 5245–54. doi:10.1038/sj.onc.1205647. PMID 12149646.
- Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G (Feb 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216.
- Lehner B, Sanderson CM (Jul 2004). "A protein interaction framework for human mRNA degradation". Genome Research. 14 (7): 1315–23. doi:10.1101/gr.2122004. PMC 442147. PMID 15231747.
- Chen Q, Qian K, Yan C (Dec 2005). "Cloning of cDNAs with PDCD2(C) domain and their expressions during apoptosis of HEK293T cells". Molecular and Cellular Biochemistry. 280 (1-2): 185–91. doi:10.1007/s11010-005-8910-z. PMID 16311922.
- Baron BW, Zeleznik-Le N, Baron MJ, Theisler C, Huo D, Krasowski MD, Thirman MJ, Baron RM, Baron JM (May 2007). "Repression of the PDCD2 gene by BCL6 and the implications for the pathogenesis of human B and T cell lymphomas". Proceedings of the National Academy of Sciences of the United States of America. 104 (18): 7449–54. doi:10.1073/pnas.0701770104. PMC 1863460. PMID 17468402.
