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Gene Review:

PAXIP1 - PAX interacting (with transcription...

Homo sapiens

Synonyms: CAGF28, CAGF29, PACIP1, PAX transactivation activation domain-interacting protein, PAX-interacting protein 1, ...

Cho, E.A. et al., Jowsey, P.A. et al., Hoffmeister, A. et al., Rademakers, R. et al., Lechner, M.S. et al., et al.

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High impact information on PAXIP1

Mutation analysis of coding exons of 29 candidate genes identified one linked synonymous mutation, g.38030G-->C in exon 10, that affected codon 626 of the PAX transactivation domain interacting protein gene (PAXIP1) [1].
Condensation of chromatin and expression of phospho-histone H3 are also affected in PTIP mutants, and this may underlie the inability of PTIP mutants to progress through mitosis [2].
Given the role of BRCT domain proteins in DNA repair and cell cycle control, we propose that PTIP is an essential element of the cell proliferation machinery, perhaps by functioning in the DNA repair pathways [2].
Trophoblast cells from PTIP mutants are more sensitive to DNA-damaging agents [2].
Homozygous PTIP mutants are developmentally retarded, disorganized, and embryonic lethal by day 9.5 of embryonic development (E9.5) [2].

Biological context of PAXIP1

Lowering hPTIP levels also increased cellular sensitivity to IR, suggesting that this protein plays a critical role in maintaining genome stability [3].
Mus musculus Pax2 transactivation domain-interacting protein (Ptip) is an essential gene required for the maintenance of genome stability, although its precise molecular role is unclear [3].
Transient transfection studies revealed that PTIP is a strong inhibitor of the trans-activation activities of Pax2A and Pax2B on the glucagon gene promoter, which was chosen as a model because it is a target of the Pax2A and Pax2B transcription factors [4].
PTIP tandem BRCT domains are responsible for phosphorylation-dependent protein localization into 53BP1- and phospho-H2AX (gamma-H2AX)-containing nuclear foci, a marker of DNA damage [5].
PTIP mutant cells appear to replicate DNA but show reduced levels of mitosis and widespread cell death by E8 [2].

Anatomical context of PAXIP1

Neither embryonic fibroblast nor embryonic stem cells from PTIP mutants proliferate in culture, suggesting a fundamental defect in cell proliferation [2].
Pax2 and PTIP co-localize in the cell nucleus to actively expressed chromatin and the nuclear matrix fraction [6].

Other interactions of PAXIP1

Human PTIP facilitates ATM-mediated activation of p53 and promotes cellular resistance to ionizing radiation [3].

Analytical, diagnostic and therapeutic context of PAXIP1

PTIP binds to Pax2 in vitro, in the yeast two-hybrid assay and in tissue culture cells [6].

References

Linkage and association studies identify a novel locus for Alzheimer disease at 7q36 in a Dutch population-based sample. Rademakers, R., Cruts, M., Sleegers, K., Dermaut, B., Theuns, J., Aulchenko, Y., Weckx, S., De Pooter, T., Van den Broeck, M., Corsmit, E., De Rijk, P., Del-Favero, J., van Swieten, J., van Duijn, C.M., Van Broeckhoven, C. Am. J. Hum. Genet. (2005) [Pubmed]
BRCT domain-containing protein PTIP is essential for progression through mitosis. Cho, E.A., Prindle, M.J., Dressler, G.R. Mol. Cell. Biol. (2003) [Pubmed]
Human PTIP facilitates ATM-mediated activation of p53 and promotes cellular resistance to ionizing radiation. Jowsey, P.A., Doherty, A.J., Rouse, J. J. Biol. Chem. (2004) [Pubmed]
The HMG-I/Y-related protein p8 binds to p300 and Pax2 trans-activation domain-interacting protein to regulate the trans-activation activity of the Pax2A and Pax2B transcription factors on the glucagon gene promoter. Hoffmeister, A., Ropolo, A., Vasseur, S., Mallo, G.V., Bodeker, H., Ritz-Laser, B., Dressler, G.R., Vaccaro, M.I., Dagorn, J.C., Moreno, S., Iovanna, J.L. J. Biol. Chem. (2002) [Pubmed]
BRCT repeats as phosphopeptide-binding modules involved in protein targeting. Manke, I.A., Lowery, D.M., Nguyen, A., Yaffe, M.B. Science (2003) [Pubmed]
PTIP, a novel BRCT domain-containing protein interacts with Pax2 and is associated with active chromatin. Lechner, M.S., Levitan, I., Dressler, G.R. Nucleic Acids Res. (2000) [Pubmed]

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