PCM-1, A 228-kD centrosome autoantigen with a distinct cell cycle distribution

Balczon, Ron; Bao, Liming; Zimmer, Warren E.

doi:10.1083/jcb.124.5.783

Cited by 142 publications

(135 citation statements)

References 24 publications

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“…In lanes 7-14 the relative strength of binding of the two probes is tested by competition with increasing concentrations of unlabelled probe corresponding to the opposite allele of rs208747 (molar excesses of competitor were 1-, 10-, 20-and 50-fold). A band is visible in lane 7 but not in lanes [8][9][10]. Similarly a band is visible in lanes 11 and 12 but not in lanes 13 and 14.…”

Section: Discussionmentioning

confidence: 71%

“…Dissociation occurs during mitosis when PCM1 is dispersed throughout the cell. 10 Immunolabelling studies performed by Kubo et al 11 found that PCM1 was present in centriolar satellites and in electron dense granules between 70 and 100 nm in diameter. These were originally thought to be scattered only around the centrosomes, but further studies proved that PCM1 was also found throughout the cytoplasm.…”

Section: Introductionmentioning

confidence: 99%

“…10 The protein appears to associate with the centrosome complex during the G 1 , S and part of the G 2 phase in the cell cycle. Dissociation occurs during mitosis when PCM1 is dispersed throughout the cell.…”

Section: Introductionmentioning

confidence: 99%

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A threonine to isoleucine missense mutation in the pericentriolar material 1 gene is strongly associated with schizophrenia

et al. 2008

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Markers at the pericentriolar material 1 gene (PCM1) have shown genetic association with schizophrenia in both a University College London (UCL) and a USA-based case-control sample. In this paper we report a statistically significant replication of the PCM1 association in a large Scottish case-control sample from Aberdeen. Resequencing of the genomic DNA from research volunteers who had inherited haplotypes associated with schizophrenia showed a threonine to isoleucine missense mutation in exon 24 which was likely to change the structure and function of PCM1 (rs370429). This mutation was found only as a heterozygote in 98 schizophrenic research subjects and controls out of 2246 case and control research subjects. Among the 98 carriers of rs370429, 67 were affected with schizophrenia. The same alleles and haplotypes were associated with schizophrenia in both the London and Aberdeen samples. Another potential aetiological base pair change in PCM1 was rs445422, which altered a splice site signal. A further mutation, rs208747, was shown by electrophoretic mobility shift assays to create or destroy a promoter transcription factor site. Five further non-synonymous changes in exons were also found. Genotyping of the new variants discovered in the UCL case-control sample strengthened the evidence for allelic and haplotypic association (P = 0.02-0.0002). Given the number and identity of the haplotypes associated with schizophrenia, further aetiological base pair changes must exist within and around the PCM1 gene. PCM1 protein has been shown to interact directly with the disrupted-in-schizophrenia 1 (DISC1) protein, BardetBiedl syndrome 4, and Huntingtin-associated protein 1, and is important in neuronal cell growth. In a separate study we found that clozapine but not haloperidol downregulated PCM1 expression in the mouse brain. We hypothesize that mutant PCM1 may be responsible for causing a subtype of schizophrenia through abnormal cell division and abnormal regeneration in dividing cells in the central nervous system. This is supported by our previous finding of orbitofrontal volumetric deficits in PCM1-associated schizophrenia patients as opposed to temporal pole deficits in non-PCM1-associated schizophrenia patients. Caution needs to be exercised in interpreting the actual biological effects of the mutations we have found without further cell biology. However, the DNA changes we have found deserve widespread genotyping in multiple case-control populations.

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Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

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A threonine to isoleucine missense mutation in the pericentriolar material 1 gene is strongly associated with schizophrenia

et al. 2008

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“…The MTUS1 gene is a newly identified candidate tumor suppressor gene [14] and the protein product of this gene has been shown to interact with angiotensin II AT2 receptor, and inhibit growth-factor-induced extracellular-regulated kinase (ERK) activation and cell proliferation [25,26]. The protein product of PCM1 gene is a centrosomal protein that exhibits a distinct cell cycle-dependent association with the centrosome complex [27], and has been showed to form fusion protein with RET protooncogene in papillary thyroid carcinoma [28], and with JAK2 in leukemia [29]. The protein product of LZTS1 contains a leucine zipper region with similarity to the DNA-binding domain of the cAMP-responsive activating transcription factor-5, and may involve in cell cycle regulation at late S-G2/M stage [30].…”

Section: Resultsmentioning

confidence: 99%

Genomic assessments of the frequent loss of heterozygosity region on 8p21.3∼p22 in head and neck squamous cell carcinoma

Pungpravat

Huang

et al. 2007

Cancer Genetics and Cytogenetics

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Most human cancers are characterized by genetic instabilities. Chromosomal aberrations include segments of allelic imbalance identifiable by loss of heterozygosity (LOH) at polymorphic loci, which may be used to implicate regions harboring tumor suppressor genes. Here we performed whole genome LOH profiling on over 40 human head and neck squamous cell carcinoma (HNSCC) cell lines. Several frequent LOH regions have been identified on chromosomal arms 3p, 4p, 4q, 5q, 8p, 9p, 10p, 11q, and 17p. A genomic region of ∼7 Mb located at 8p22-p21.3 exhibits the most frequent LOH (87.9%), which suggested that this region harbors important tumor suppressor gene(s). Mitochondrial tumor suppressor gene 1 (MTUS1) is a recently identified candidate tumor suppressor gene that resides in this region. Consistent down-regulation in expression was observed in HNSCC for MTUS1 as measured by real-time quantitative RT-PCR. Sequence analysis of MTUS1 gene in HNSCC revealed several important sequence variants in the exon regions of this gene. Thus, our results suggested that MTUS1 is one of the candidate tumor suppressor gene(s) reside in 8p22-p21.3 for HNSCC. The identification of these candidate genes will facilitate the understanding of tumorigenesis of HNSCC. Further studies are needed to functionally evaluate those candidate genes.

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“…One component is PCM1, a 228-kDa autoantigen recognized by anti-centrosome serum 4,8 . PCM1 has a dynamic cellular distribution, localizing with centrosomal satellites throughout the cell cycle except during metaphase and anaphase, when it becomes cytosolic 8,9 .…”

mentioning

confidence: 99%

The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression

et al. 2004

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BBS4 is one of several proteins that cause Bardet-Biedl syndrome (BBS), a multisystemic disorder of genetic and clinical complexity. Here we show that BBS4 localizes to the centriolar satellites of centrosomes and basal bodies of primary cilia, where it functions as an adaptor of the p150 glued subunit of the dynein transport machinery to recruit PCM1 (pericentriolar material 1 protein) and its associated cargo to the satellites. Silencing of BBS4 induces PCM1 mislocalization and concomitant deanchoring of centrosomal microtubules, arrest in cell division and apoptotic cell death. Expression of two truncated forms of BBS4 that are similar to those found in some individuals with BBS had a similar effect on PCM1 and microtubules. Our findings indicate that defective targeting or anchoring of pericentriolar proteins and microtubule disorganization contribute to the BBS phenotype and provide new insights into possible causes of familial obesity, diabetes and retinal degeneration.

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PCM-1, A 228-kD centrosome autoantigen with a distinct cell cycle distribution

Cited by 142 publications

References 24 publications

A threonine to isoleucine missense mutation in the pericentriolar material 1 gene is strongly associated with schizophrenia

A threonine to isoleucine missense mutation in the pericentriolar material 1 gene is strongly associated with schizophrenia

Genomic assessments of the frequent loss of heterozygosity region on 8p21.3∼p22 in head and neck squamous cell carcinoma

The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression

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