Disease relevance of CDC2L1

• To determine whether CDC2L1 mutation is involved in melanoma development, we examined 20 melanoma cell lines and 11 members of melanoma-prone families linked to chromosome 1p36 [1].
• Thus, we showed that the neuroblastoma tumour suppressor critical region on 1p in our material is defined by loci D1S244 and D1S80 and that the CDC2L1 locus is distal to the critical region [2].

High impact information on CDC2L1

• Thus, proper regulation of p58 protein kinase is essential for normal cell cycle progression in these cells [3].
• Due to its relatedness to p34CDC2, the human p58 cDNA was overexpressed in CHO cells to determine the effect on the cell cycle [3].
• However, the actual cellular mechanism that regulates cell growth, differentiation, and development by CLK/STY remains unclear [4].
• Here we show that a functionally conserved CLK/STY kinase exists in Schizosaccharomyces pombe, and this orthologue, called Kic1, regulates the cell surface and septum formation as well as a late step in cytokinesis [4].
• The three members of the Clk family of kinases (Clk1, 2, and 3) have been shown to undergo conserved alternative splicing to generate catalytically active (Clk) and inactive (ClkT) isoforms [5].

Chemical compound and disease context of CDC2L1

• These results indicate that mutations are rare in the CDC2L1 gene in these melanoma cell lines and melanoma families and that the aberrant cytosine methylation of the CDC2L1 CpG island is not the mechanism of CDC2L1 repression in melanoma [1].

Biological context of CDC2L1

• We also observed mutations in the 5' promoter region of the CDC2L1 gene in four different cell lines relative to normal melanocytes using PCR-SSCP analysis and direct DNA sequencing [6].
• The two genes encoding the PITSLRE protein kinase isoforms, CDC2L1 and CDC2L2, are localized to human chromosome band 1p36 [6].
• No aberrant methylation of the CDC2L1 CpG island in the promoter region was observed by sodium bisulfite genomic sequencing [1].
• The 4 variants were located within or beside the conserved binding sites of transcription factors TCF11, MZF1 and TAAC box, indicating their potential effects on the regulation of CDC2L1 expression [1].
• Using a DNA sequence polymorphism, we showed, in a primary tumour with an interstitial allelic deletion, that this tumour had both alleles of the CDC2L1 locus retained in the tumour [2].

Anatomical context of CDC2L1

• A major component of the cortical myoplasm, p58, is co-localized along the microtubules emanating from the sperm aster [7].

Associations of CDC2L1 with chemical compounds

• The objective of the present study was to elucidate the structural characteristics of the adenosine-binding site of four major kinase groups, AGC (PKA, PKG, and PKC families), CaMK (calcium/calmodulin-dependent protein kinases), CMGC (CDK, MAPK, GSK3, and CLK families), and TK (tyrosine kinases) [8].
• However, binding of alanine to p58 did not block the association of p58 to form the tetrameric pyruvate kinase [9].
• Analysis of the competitive binding data indicated that alanine, at the physiological concentration, is a non-competitive inhibitor of T3 binding to p58 [9].

Other interactions of CDC2L1

• Four different probes from the 1p36 region, the E2F2, NPPA, D1S160, and CDC2L1 loci were used for detection of 1p abnormalities [10].

Analytical, diagnostic and therapeutic context of CDC2L1

• To determine the molecular consequences of the recurrent involvement of the 1p36 region, we examined metaphases containing 1p36 abnormalities from 31 specimens derived from 26 patients for the possible deletion of CDC2L1 by fluorescence in situ hybridization (FISH) using the TP58clk-1 DNA probe [11].
• The relative abundance and size of the two p58 mRNA species detected are consistent with the 58- and 55-kDa proteins detected by in vitro translation of B. bigemina poly(A)+ mRNA by immunoprecipitation with an anti-p58 monospecific antibodies [12].
• Four copies of the gene encoding the merozoite surface protein p58 from the protozoan hemoparasite Babesia bigemina were amplified from genomic DNA by polymerase chain reaction (PCR) techniques, molecularly cloned and subjected to DNA sequence analysis [12].

References