CENPJ

Template:PBB Centromere protein J is a protein that in humans is encoded by the CENPJ gene. 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.

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.

Model organisms

Cenpj knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Abnormal
Recessive lethal study	Normal
Homozygous Fertility	Normal
Body weight	Abnormal
Anxiety	Abnormal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Abnormal
Indirect calorimetry	Abnormal
Glucose tolerance test	Abnormal
Auditory brainstem response	Normal
DEXA	Abnormal
Radiography	Abnormal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Abnormal
Haematology	Normal
Peripheral blood lymphocytes	Abnormal
Micronucleus test	Abnormal
Heart weight	Normal
Brain histopathology	Abnormal
Eye Histopathology	Abnormal
Salmonella infection	Normal
Citrobacter infection	Normal
All tests and analysis from

Model organisms have been used in the study of CENPJ function. A conditional knockout mouse line, called Cenpj^{tm1a(EUCOMM)Wtsi} 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.

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. 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.

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.

Interactions

CENPJ has been shown to interact with EPB41.

Further reading

• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• Iouzalen N, Andreae S, Hannier S, Triebel F (2001). "LAP, a lymphocyte activation gene-3 (LAG-3)-associated protein that binds to a repeated EP motif in the intracellular region of LAG-3, may participate in the down-regulation of the CD3/TCR activation pathway". Eur. J. Immunol. 31 (10): 2885–91. doi:10.1002/1521-4141(2001010)31:10<2885::AID-IMMU2885>3.0.CO;2-2. PMID 11592063.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• Tchernev VT, Mansfield TA, Giot L; et al. (2002). "The Chediak-Higashi protein interacts with SNARE complex and signal transduction proteins". Mol. Med. 8 (1): 56–64. PMC 2039936. PMID 11984006. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Peng B, Sutherland KD, Sum EY; et al. (2003). "CPAP is a novel stat5-interacting cofactor that augments stat5-mediated transcriptional activity". Mol. Endocrinol. 16 (9): 2019–33. doi:10.1210/me.2002-0108. PMID 12198240. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Leal GF, Roberts E, Silva EO; et al. (2003). "A novel locus for autosomal recessive primary microcephaly (MCPH6) maps to 13q12.2". J. Med. Genet. 40 (7): 540–2. doi:10.1136/jmg.40.7.540. PMC 1735531. PMID 12843329. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Ota T, Suzuki Y, Nishikawa T; et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Hung LY, Chen HL, Chang CW; et al. (2004). "Identification of a Novel Microtubule-destabilizing Motif in CPAP That Binds to Tubulin Heterodimers and Inhibits Microtubule Assembly". Mol. Biol. Cell. 15 (6): 2697–706. doi:10.1091/mbc.E04-02-0121. PMC 420094. PMID 15047868. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Dunham A, Matthews LH, Burton J; et al. (2004). "The DNA sequence and analysis of human chromosome 13". Nature. 428 (6982): 522–8. doi:10.1038/nature02379. PMC 2665288. PMID 15057823. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Gerhard DS, Wagner L, Feingold EA; et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Koyanagi M, Hijikata M, Watashi K; et al. (2005). "Centrosomal P4.1-associated protein is a new member of transcriptional coactivators for nuclear factor-kappaB". J. Biol. Chem. 280 (13): 12430–7. doi:10.1074/jbc.M410420200. PMID 15687488. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
• Bond J, Roberts E, Springell K; et al. (2005). "A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size". Nat. Genet. 37 (4): 353–5. doi:10.1038/ng1539. PMID 15793586. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Cho JH, Chang CJ, Chen CY, Tang TK (2006). "Depletion of CPAP by RNAi disrupts centrosome integrity and induces multipolar spindles". Biochem. Biophys. Res. Commun. 339 (3): 742–7. doi:10.1016/j.bbrc.2005.11.074. PMID 16316625.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• Kimura K, Wakamatsu A, Suzuki Y; et al. (2006). "Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Chen CY, Olayioye MA, Lindeman GJ, Tang TK (2006). "CPAP interacts with 14-3-3 in a cell cycle-dependent manner". Biochem. Biophys. Res. Commun. 342 (4): 1203–10. doi:10.1016/j.bbrc.2006.02.089. PMID 16516142.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• Evans PD, Vallender EJ, Lahn BT (2006). "Molecular evolution of the brain size regulator genes CDK5RAP2 and CENPJ". Gene. 375: 75–9. doi:10.1016/j.gene.2006.02.019. PMID 16631324.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• Lim J, Hao T, Shaw C; et al. (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• 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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)