Disease relevance of CKM

• Recent genetic linkage analyses have mapped the myotonic dystrophy locus to the region of 19q13.2-13.3 lying distal to the gene for creatine kinase subunit M (CKM) [1].
• The activities of CS, total CK, and CKM in papillary muscle from patients operated on for mitral regurgitation did not differ from that of healthy papillary muscle [2].
• We have generated two replication-defective adenovirus recombinants (AV) in which the reporter gene (either firefly luciferase or E. coli beta-galactosidase) was driven by a truncated (1.35 kb) muscle creatine kinase (MCK) promoter/enhancer or by the fast troponin I (TnI) promoter/enhancer [3].
• It is concluded that in most tumours there is a decrease in the expression of type B- and type M-CK subunits, whereas in lung carcinoid the expression of type B-CK activity increases [4].
• Both the UKM-derived normalized protein catabolic rate (nPCR) and the CKM-derived estimate of lean body mass (LBM) may also provide important information in critically ill acute renal failure (ARF) patients [5].

Psychiatry related information on CKM

• CONCLUSION: The present results provide further support for the notion that the CKMM gene, or some gene in close linkage disequilibrium with it, may contribute to individual differences in the VO2max response to endurance training [6].

High impact information on CKM

• Wild-type p53 protein was shown to bind specifically to DNA sequences within SV40 (Bargonetti et al. 1991), the human ribosomal gene cluster (RGC) (Kern et al. 1991a), and the murine muscle creatine kinase gene (MCK) (Zambetti et al. 1992) [7].
• Myogenin translated in vitro does not exhibit detectable DNA binding activity; however, when dimerized with the ubiquitous enhancer-binding factor E12, it acquires high affinity for an element in the core of the muscle creatine kinase (MCK) enhancer that is conserved among many muscle-specific genes [8].
• Results were combined with data from CHEF and field inversion-gel-electrophoresis separation of large-sized DNA restriction fragments to establish a map localizing both DNA-repair genes and the CKMM gene within the same 250 kb of DNA, the order being cen-CKMM-ERCC2-ERCC1-ter, with APOC2 being at more than 260 kb proximal to CKMM [9].
• Transcriptional start sites of the CKMM and DNA-repair genes are all on the telomeric side of the genes [9].
• The region of human chromosome 19 which includes the myotonic dystrophy locus (DM) has recently been redefined by the tight linkage between it and the gene for muscle-specific creatine kinase (CKMM), which lies just proximal to DM [10].

Chemical compound and disease context of CKM

• BACKGROUND: Urea kinetic modeling (UKM) and creatinine (Cr) kinetic modeling (CKM) are used in the nutritional evaluation of end-stage renal disease (ESRD) patients [5].
• Staining with antimyoglobin and anti-CKM was much less satisfactory, with positivity rates of 17 of 37 and 11 of 57, respectively, in formalin-fixed rhabdomyosarcomas [11].

Biological context of CKM

• The human chromosome 19 synteny of ERCC2 and CKM thus appears to be conserved in Xiphophorus, while other genes located nearby on human chromosome 19 are in a separate linkage group in this fish [12].
• Thus the earlier assignment of the gene coding for the CKBB isozyme to chromosome 14 was confirmed by molecular means, as was the provisional assignment of CKMM to the long arm of chromosome 19 [13].
• By using a dog heart MCK cDNA-derived probe, the 7.0-kb EcoRI fragment from one cross-hybridizing genomic clone was isolated and its complete nucleotide sequence determined [14].
• This indicates that the loss of cytoplasm and the commencement of M-CK isoform synthesis are related events during the last phase of spermatogenesis, also that the incidence of spermatozoa with incomplete cellular maturation is higher in oligospermic specimens [15].
• In order to produce other markers useful for DM, we have screened genomic DNA libraries constructed from cell line 20XP3542-1-4, which contains 20 to 30 Mb of human material including APOC2 and CKM [16].

Anatomical context of CKM

• Probes for the 3'-noncoding sequences of human CKBB and CKMM hybridized concordantly only to DNAs from somatic cell hybrids containing chromosomes 14 and 19, respectively [13].
• PURPOSE: This study examined 12 wk of creatine (Cr) supplementation and heavy resistance training on skeletal muscle creatine kinase (M-CK) mRNA expression and the mRNA and protein expression of the myogenic regulatory factors Myo-D, myogenin, MFR-4, and Myf5 [17].
• While muscle CK (CKM) is expressed almost exclusively in adult skeletal and cardiac muscle, brain CK (CKB) expression is more widespread and is highest in brain glial cells [18].
• An amplicon vector, HyMD, containing the full-length mouse dystrophin cDNA and its muscle creatine kinase (MCK) promoter-enhancer, with a total size of 26 kb, was constructed and used to transduce mdx mouse myotubes [19].
• The M-CK isoform was plasma membrane associated and predominately localized to the apical surface [20].

Associations of CKM with chemical compounds

• Statistically significant evidence for linkage was found only for ERCC2L1 and CKM (muscle creatine kinase), with a total of 41 parents and 2 recombinants (4.7% recombination, chi 2 = 35.37, P less than 0.001); no evidence for linkage to GPI and PEPD in linkage group IV was detected [12].
• Thus, the functional efficacy of bound MM-CK to regulate adenine nucleotide turnover within the myofibrillar compartment seems to be specific for muscles expressing M-CK as an integral part of the sarcomere [21].
• A novel NcoI polymorphism has been detected in the 3' untranslated region of the creatinine kinase (CKM) gene [22].
• Tight linkage was also demonstrated for CKMM and the gene for apolipoprotein C2 (ApoC2) [23].

Regulatory relationships of CKM

• (2) Efficient coupling of MM-CK to myosin ATPase is seen in adult mammalian striated muscles but not in frog and bird heart where B-CK is expressed instead of M-CK [21].

Other interactions of CKM

• In the present work, we examined whether in spermatozoa, similar to muscle, there is a change in the synthesis of B-CK and M-CK isoforms during cellular differentiation [15].
• CONCLUSION: When combined with heavy resistance training, Cr supplementation increases M-CK mRNA expression, likely due to concomitant increases in the expression of myogenin and MRF-4 [17].
• A novel polymorphic DNA marker, pEO.8, has been isolated from a chromosome 19 ERCC1-containing cosmid that maps to a 300-kb NotI fragment encompassing both CKM and ERCC1 [1].
• Linkage studies in DM families using RFLPs as polymorphic markers refined the mapping position to 19q13.1-13.2 distal to the BCL3, apoCII, CKM and ERCCI genes [24].
• Four of the clones from chromosome 19 map distal to CKM and two of these clones (D19S62 and D19S63) are closely linked to DM [16].

Analytical, diagnostic and therapeutic context of CKM

• The cardiac CKB, but not CKM mRNA level, was twofold higher using the quantitative PCR method [25].
• Thus, CKMM is a useful probe for carrier detection studies in presymptomatic individuals as well as for prenatal diagnosis [26].
• However, by immunoblotting, non-denaturing gel electrophoresis and immunohistochemistry, the presence of the M-CK isoform of creatine kinase was also detected [20].
• Here we demonstrate, by filter binding and gel mobility-shift assays, that wild-type p53 binds with similar affinities to MCK and RGC sites but less tightly to the SV40 site [7].
• Blot analysis of total cell RNA from differentiating myogenic cell cultures showed accumulation of M-CK mRNA in cultures older than 42 hr but not in young little-differentiated cultures [27].

References