Disease relevance of PCNT

• Our data suggest that children with post-varicella ataxia have unique autoantibody reactivity to pericentrin [1].
• In addition, we analyzed glioma U251 cells, which co-expressed MT1-MMP with the wild type murine pericentrin and the D948G mutant [2].
• Divergent localizations of gamma-tubulin and pericentrin suggest a differential distribution of these 2 centrosome-associated proteins in glioblastoma cell lines [3].
• Upon infection of enucleated cells with Cy3-labeled Ad, the majority of Ad capsid trafficked to a discrete, centrally located site which colocalized with pericentrin, a component of the MTOC [4].
• We examined 34 CML samples including CD 34+Ph+cells of 18 newly diagnosed patients (chronic phase (CP)) and 16 blast crisis (BC) specimens by using a centrosome-specific antibody to pericentrin [5].

High impact information on PCNT

• We conclude that Pcnt, IFTs, and PC2 form a complex in vertebrate cells that is required for assembly of primary cilia and possibly motile cilia and flagella [6].
• Formation of new centrosomes occurs in two steps: approximately 5-8 h after ablation, clouds of pericentriolar material (PCM) containing gamma-tubulin and pericentrin appear in the cell [7].
• Numerous coiled-coil structures were predicted from AKAP450, and weak homology to pericentrin, giantin and other structural proteins was observed [8].
• The pericentriolar components, gamma tubulin and dynactin, are lost from centrosomes, but pericentrin localization persists [9].
• In mitotic human breast carcinoma cells containing abundant centrosome-like structures, kendrin is found only at centrosomes associated with spindle microtubules [10].

Biological context of PCNT

• With PCR amplification, Southern blot analysis, and FISH, we have mapped this presumed human pericentrin gene (PCNT) to the long arm of chromosome 21 between marker PFKL and 21qter [11].
• Antibodies against pericentrin-B stain centrosomes at all stages of the cell cycle, and pericentrin-B remains associated with centrosomes following microtubule depolymerization [12].
• N-terminal regions of kendrin share significant sequence homology with pericentrin, a previously identified murine centrosome component known to interact with gamma-tubulin [10].
• We demonstrate that both RII and the catalytic subunit of PKA coimmunoprecipitate with pericentrin isolated from HEK-293 cell extracts and that PKA catalytic activity is enriched in pericentrin immunoprecipitates [13].
• Extensive sequence homology between the mouse chromosome 10 region encoding pericentrin and the human chromosome 21 region encoding kendrin indicates that these proteins are encoded by syntenic loci [14].

Anatomical context of PCNT

• Immunocytochemical analysis revealed the colocalization of DISC1 and kendrin to the centrosome [15].
• These results imply that CG-NAP and kendrin provide sites for microtubule nucleation in the mammalian centrosome by anchoring gamma-TuRC [16].
• Using immunofluorescence analysis with gamma-tubulin and pericentrin antibodies, paraffin-embedded sections from 40 malignant biliary diseases including gallbladder cancers (GC; n = 13), intrahepatic cholangiocellular carcinoma (CCC; n = 19), and extrahepatic bile duct cancers (BDC; n = 8) were examined [17].
• Immunochemical evidence indicates that at least several of the proteins found in mammalian centrosomes, gamma-tubulin, centrin, pericentrin, and polypeptides recognized by the monoclonal antibodies MPM-2, 6C6, and C9 also recognize putative lower land plant MTOCs, indicating shared mechanisms of nucleation/organization in plants and animals [18].
• We show that the centrosome/aggresome-related proteins gamma-tubulin and pericentrin display an aggresome-like distribution in Lewy bodies in PD and DLB [19].

Physical interactions of PCNT

• DISC1 localizes to the centrosome by binding to kendrin [15].
• Furthermore, Nudel can interact with pericentrin independently of dynein [20].

Other interactions of PCNT

• Residues 446-533 of DISC1 were essential for the interaction with kendrin [15].
• Immunodepletion of neither pericentrin-B nor PCM-1 from cellular extracts inhibited the ability of salt-stripped centrosomes to recover microtubule nucleation potential, demonstrating that neither protein plays a key role in microtubule nucleation processes [12].
• Despite its association with gamma-TuRC anchoring proteins CG-NAP and Kendrin, Cep55 is not required for microtubule nucleation [21].
• We constructed three TCDD exposure indices from the questionnaire data: the number of days of skin exposure (DAYS), the percentage of skin area exposed (PCNT), and a combined index (SRI) which was the product of these and the concentration of TCDD in the herbicide [22].
• The amplified centrosomes co-localized with centrosome markers gamma-tubulin, centrin-2 and kendrin as well as endogenous CG-NAP [23].

Analytical, diagnostic and therapeutic context of PCNT

• The interaction between DISC1 and kendrin in mammalian cells was demonstrated by an immunoprecipitation assay [15].
• The distribution of pericentrin in the cerebellum was studied by indirect immunofluorescence (IIF) using rabbit antibodies to the recombinant protein [1].
• Biochemical sedimentation and/or confocal microscopy analyses showed that the pericentriolar components gamma-tubulin and pericentrin remained at centrosomes, whereas the distributions of proteins p150Glued and the dynein intermediate chain were altered [24].
• With pericentrin immunohistochemistry, maximum centrosomal aberration levels >35% were detectable in 92 of the 103 breast carcinomas (89%) [25].
• Two pericentrin transcripts of 9.5 and 6.9kb were recognized on the mouse tissue Northern blots, while a cRNA probe for a 5'-terminal sequence shared by pericentrin A and B failed to hybridize to the 6.9-kb message [26].

References