CENPJ

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Centromere protein J
Identifiers
Symbols CENPJ ; BM032; CENP-J; CPAP; LAP; LIP1; MCPH6; SASS4; SCKL4; Sas-4
External IDs OMIM609279 MGI2684927 HomoloGene10204 GeneCards: CENPJ Gene
RNA expression pattern
PBB GE CENPJ 220885 s at tn.png
PBB GE CENPJ gnf1h01806 at tn.png
PBB GE CENPJ gnf1h02733 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 55835 219103
Ensembl ENSG00000151849 ENSMUSG00000064128
UniProt Q9HC77 Q569L8
RefSeq (mRNA) NM_018451 NM_001014996
RefSeq (protein) NP_060921 NP_001014996
Location (UCSC) Chr 13:
25.46 – 25.5 Mb
Chr 14:
56.53 – 56.57 Mb
PubMed search [1] [2]

Centromere protein J is a protein that in humans is encoded by the CENPJ gene.[1][2] It is also known as centrosomal P4.1-associated protein (CPAP). During cell division, this protein plays a structural role in the maintenance of centrosome integrity and normal spindle morphology, and it is involved in microtubule disassembly at the centrosome. This protein can function as a transcriptional coactivator in the Stat5 signaling pathway, and also as a coactivator of NF-kappaB-mediated transcription, likely via its interaction with the coactivator p300/CREB-binding protein. Mutations in this gene are associated with Seckel syndrome and primary autosomal recessive microcephaly, a disorder characterized by severely reduced brain size and mental retardation.[2][3][4]

The Drosophila ortholog, sas-4, has been shown to be a scaffold for a cytoplasmic complex of Cnn, Asl, CP-190, tubulin and D-PLP (similar to the human proteins PCNT and AKAP9). These complexes are then anchored at the centriole to begin formation of the centrosome.[5]

Model organisms[edit]

Model organisms have been used in the study of CENPJ function. A conditional knockout mouse line, called Cenpjtm1a(EUCOMM)Wtsi[19][20] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[21][22][23]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[17][24] Twenty five tests were carried out on mutant mice and thirteen significant abnormalities were observed. Homozygous mutants were subviable, had a decreased body weight, abnormal open field, body composition, X-ray imaging, peripheral blood lymphocytes and indirect calorimetry parameters, abnormal head, genitalia and tail morphology, an impaired glucose tolerance, hypoalbuminemia, a 1.5 fold increase in micronuclei, a reduction in dentate gyrus length and abnormal corneal epithelium and endothelium. [17]

A more detailed analysis revealed this mutant to model a number of aspects of Seckel syndrome (type 4). The authors concluded that, "increased cell death due to mitotic failure during embryonic development is likely to contribute to the proportionate dwarfism" that is characteristic of the disorder.[25]

Interactions[edit]

CENPJ has been shown to interact with EPB41.[1]

References[edit]

  1. ^ a b Hung LY, Tang CJ, Tang TK (Oct 2000). "Protein 4.1 R-135 Interacts with a Novel Centrosomal Protein (CPAP) Which Is Associated with the γ-Tubulin Complex". Mol Cell Biol 20 (20): 7813–25. doi:10.1128/MCB.20.20.7813-7825.2000. PMC 86375. PMID 11003675. 
  2. ^ a b "Entrez Gene: CENPJ centromere protein J". 
  3. ^ Al-Dosari MS, Shaheen R, Colak D, Alkuraya FS (2010). "Novel CENPJ mutation causes Seckel syndrome.". J Med Genet 47 (6): 411–4. doi:10.1136/jmg.2009.076646. PMID 20522431. 
  4. ^ Gul A, Hassan MJ, Hussain S, et al. (2006). "A novel deletion mutation in CENPJ gene in a Pakistani family with autosomal recessive primary microcephaly". J. Hum. Genet. 51 (9): 760–4. doi:10.1007/s10038-006-0017-1. PMID 16900296. 
  5. ^ Gopalakrishnan J, Mennella V, Blachon S, Zhai B, Smith AH, Megraw TL, Nicastro D, Gygi SP, Agard DA, Avidor-Reiss T (2011). "Sas-4 provides a scaffold for cytoplasmic complexes and tethers them in a centrosome". Nat Commun 2: 359. doi:10.1038/ncomms1367. PMID 21694707. 
  6. ^ "Body weight data for Cenpj". Wellcome Trust Sanger Institute. 
  7. ^ "Anxiety data for Cenpj". Wellcome Trust Sanger Institute. 
  8. ^ "Dysmorphology data for Cenpj". Wellcome Trust Sanger Institute. 
  9. ^ "Indirect calorimetry data for Cenpj". Wellcome Trust Sanger Institute. 
  10. ^ "Glucose tolerance test data for Cenpj". Wellcome Trust Sanger Institute. 
  11. ^ "DEXA data for Cenpj". Wellcome Trust Sanger Institute. 
  12. ^ "Radiography data for Cenpj". Wellcome Trust Sanger Institute. 
  13. ^ "Clinical chemistry data for Cenpj". Wellcome Trust Sanger Institute. 
  14. ^ "Peripheral blood lymphocytes data for Cenpj". Wellcome Trust Sanger Institute. 
  15. ^ "Salmonella infection data for Cenpj". Wellcome Trust Sanger Institute. 
  16. ^ "Citrobacter infection data for Cenpj". Wellcome Trust Sanger Institute. 
  17. ^ a b c 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. 
  18. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  19. ^ "International Knockout Mouse Consortium". 
  20. ^ "Mouse Genome Informatics". 
  21. ^ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.  edit
  22. ^ Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  23. ^ Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. 
  24. ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353. 
  25. ^ McIntyre RE, Lakshminarasimhan Chavali P, Ismail O, Carragher DM, Sanchez-Andrade G, Forment JV et al. (2012). "Disruption of mouse cenpj, a regulator of centriole biogenesis, phenocopies seckel syndrome.". PLoS Genet 8 (11): e1003022. doi:10.1371/journal.pgen.1003022. PMC 3499256. PMID 23166506. 

Further reading[edit]