Disease relevance of PCCB

• Mutations in the PCCA (alpha subunit) or PCCB (beta subunit) gene can cause the inherited metabolic disease propionic acidemia (PA), which can be life threatening in the neonatal period [1].
• Other PCCB mutants (R165W, E168K, D178H, P228L, and R410W) that are PCC deficient in patient-derived fibroblasts, were found to be capable of expressing wild-type level PCC activity when assembled in our chaperone-assisted E. coli expression system [2].
• In all cases, the levels of mRNA were lower in colorectal cancers than in normal mucosae, the decrease being always more marked for PCCB than for PCCA [3].

High impact information on PCCB

• PCC consists of two subunits, alpha and beta, encoded by the PCCA and PCCB genes, respectively [4].
• Lack of data on the genomic structure of PCCB has been a significant impediment to full characterization of PCCB mutant chromosomes [1].
• About two-thirds of fibroblast lines from patients with mutations in the PCCB (beta-subunit) gene show interallelic complementation in cell fusion experiments (the pccB and pccC subgroups of the pccBC major group defining beta-subunit mutations, where pccB x pccC fusions show complementation) [5].
• Expression of the MCCB and PCCB chains that do not carry the biotin-binding motif did not change significantly; we speculate that expression of the biotin-binding chains of biotin-dependent carboxylases is more responsive to biotin status changes [6].
• We have also analysed the effect of mutations c.653A>G and IVS10-11del6 in the PCCB gene present in heterozygous patients with mild phenotype [7].

Chemical compound and disease context of PCCB

• Having observed a high biotin content in colon mucosae and a low content in colorectal-cancer cells, we then studied the transcription levels of PCCA and PCCB genes in 9 colorectal cancers and the corresponding mucosae [3].

Biological context of PCCB

• By use of a panel of somatic mouse-human hybrids, the human gene encoding the alpha polypeptide (PCCA) was localized to chromosome 13, while the gene encoding the beta polypeptide (PCCB) was assigned to chromosome 3 [8].
• We have proved the pathogenicity of R67S, R165Q and G112D mutation in PCCB gene, expressed for the first time in this work [9].
• We present an initial characterization of 13 mutations located in exons 1, 3-7, and 12-14 of PCCB [2].
• Cell fusion experiments have revealed two complementation groups, pccA and pccB, corresponding to defects of the PCCA (alpha-subunit) and PCCB (beta-subunit) genes, respectively [10].
• A novel splicing mutation in propionic acidemia associated with a tetranucleotide direct repeat in the PCCB gene [11].

Anatomical context of PCCB

• Functional analysis of PCCB mutations causing propionic acidemia based on expression studies in deficient human skin fibroblasts [9].
• We have used a PCCB-deficient transformed fibroblast cell line to target the wild-type and mutant proteins to their physiological situation, analysing the effect of the mutations on PCC activity and protein stability [9].

Associations of PCCB with chemical compounds

• Isolation of cDNA clones coding for the alpha and beta chains of human propionyl-CoA carboxylase: chromosomal assignments and DNA polymorphisms associated with PCCA and PCCB genes [8].
• One of these is propionate, which is metabolized through carboxylation by propionyl-CoA carboxylase (PCC), an enzyme encoded by 2 genes, PCCA and PCCB [3].
• Mutations in the PCCA or PCCB genes coding for alpha and beta subunits of propionyl CoA carboxylase can cause propionic acidemia [12].

Other interactions of PCCB

• We demonstrate the reliability of this method for identification of the defective PCC gene in order to unequivocally approach the mutational analysis in the corresponding PCCA and PCCB genes [13].
• SLC25A36, PCCB, and FNDC6 are of lesser interest because of moderate expression and changes in expression [14].

Analytical, diagnostic and therapeutic context of PCCB

• Subjects were screened for defects affecting the PCCB gene by direct sequencing from genomic PCR products, restriction digests and mRNA analysis by RT-PCR [15].
• The mRNA of PCCB gene in T428I and 1527del3 homozygotes were normal but in Western blot analysis, the betaPCC-subunit was only absent in 1527del3 homozygote patient suggesting different molecular pathology [16].

References