CENPJ

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

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

Model organisms
is_associated_with::Model organisms have been used in the study of CENPJ function. A conditional is_associated_with::knockout mouse line, called Cenpjtm1a(EUCOMM)Wtsi was generated as part of the is_associated_with::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 is_associated_with::phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on is_associated_with::mutant mice and thirteen significant abnormalities were observed. is_associated_with::Homozygous mutants were subviable, had a decreased body weight, abnormal open field, body composition, X-ray imaging, peripheral blood lymphocytes and is_associated_with::indirect calorimetry parameters, abnormal head, genitalia and tail morphology, an impaired is_associated_with::glucose tolerance, is_associated_with::hypoalbuminemia, a 1.5 fold increase in micronuclei, a reduction in is_associated_with::dentate gyrus length and abnormal is_associated_with::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 is_associated_with::embryonic development is likely to contribute to the proportionate is_associated_with::dwarfism" that is characteristic of the disorder.

Interactions
CENPJ has been shown to interact with is_associated_with::EPB41.