Disease relevance of CDK5RAP1

• METHODS: The COS-1 cells and Escherichia coli were used to express the P. americana C42 allergen [1].
• Sera of some patients with systematic lupus erythematosus (SLE) contain IgG autoantibodies (F-42) which have been shown to stabilize the cell bound classical pathway C3 convertase of complement, C42 [2].
• These observations, together with the results of our previous report, indicate that the binding of C56, generated from the activation of C5 by C42 (without C3), to EAC142 may be the initial step of membrane attack complex formation in C3-independent immune hemolysis [3].

High impact information on CDK5RAP1

• The C42 enzyme can be replaced by trypsin, so that bridging units may consist of C3 + C42, C5 + C42 OR C3 + trypsin, and C5 + trypsin [4].
• The susceptibility of the PNH cell to complement lysis because of an increased fixation of C3 to its membrane is not due to a difference in membrane-associated accelerator of the decay of the C42 complex [5].
• C42, and the relative amount of inhibitory activity was similar in normal and PNH membranes [5].
• Here we show that one of these proteins, called C42, specifically inhibits the activation of Cdk5 by Nck5a [6].
• When tonsil lymphocytes, which contain between 30 and 60% of CR1-bearing B cells, are incubated with the red cell complement intermediate EAC14oxy2lim or EAC14oxy23lim, they inhibit both C42 and C423 in a dose-dependent manner [7].

Biological context of CDK5RAP1

• Two novel splice variants of CDK5RAP1, named CDK5RAP1_v3 and CDK5RAP1_v4, were isolated through the large-scale sequencing analysis of a human fetal brain cDNA library [8].
• Sequence homology searches have suggested that the C48 protein is marginally related to restin protein, whereas the C42 protein has homologues of unknown function in Caenorhabditis elegans and Arabidopsis thaliana [9].
• This raises the possibility that in the presence of nucleotides, NBD1 and NBD2 dimerize to induce the conformational change and that the dimerization enables C42 to gain access to both NBDs [10].
• Our results showed that substitutions of putative active site residues; Q36, C42, H174, and N204 resulted in complete loss of falcipain-2 activity, while W206 and D155 mutants retained partial/complete activity in comparison to the wild type falcipain-2 [11].
• Homology modeling data also corroborate the results of mutagenesis; Q36, C42, H174, N204, and W206 residues form the active site loop of the enzyme and D155 lie outside the active pocket [11].

Anatomical context of CDK5RAP1

• CONCLUSIONS: The biologically highly reactive recombinant C42 produced in the COS-1 cell provides an alternative expression system and will facilitate studies on the immune response of asthma patients to cockroach allergens [1].
• A cDNA clone (called C42) was isolated from a cDNA library made from poly(A)+ RNA obtained from HuIFN-gamma-treated human fibroblasts [12].
• Histamine, by inhibiting the production of C4, C2, and C3 and factor B by mononuclear phagocytes, inhibits further C3 and C5 cleavage by restricting the formation of C42, C423b and C3bBbP [13].
• Thus histamine, released from basophils or mast cells by the C3 and C5 cleavage products C3a and C5a respectively, may exert a negative feedback on further C3 and C5 cleavage by limiting the formation of the C3 (C42) and C5 (C423b) convertases [14].

Associations of CDK5RAP1 with chemical compounds

• In order to determine whether C4-binding protein was capable of reversing stabilization of C42, stabilized and unstabilized cell-bound C42 were exposed to purified C4-bp and the convertase activity was assessed [15].
• The observed enzymatic activity of C2 was found to be relevant to the function of C2 in the C42 complex, since AcGlyLysOMe competitively inhibited the C42 mediated cleavage of C3 in free solution and the C42 dependent binding of C3 to cells [16].
• In an effort to assess the role of C42, it has been changed to serine and alanine by site-directed mutagenesis [17].
• This study aimed to investigate the expression of a recombinant American cockroach (Periplaneta americana) Per a 1, C42, allergen in mammalian COS-1 cells [1].
• Both, binding of C5 to surface-fixed C3b and cleavage of C5 by convertases C42 and C3bBb, are also inhibited in the presence of propamidine [18].

Other interactions of CDK5RAP1

• The full-length forms of these three novel proteins, designated C42, C48 and C53, have a molecular mass of 66, 24, and 57 kDa, respectively [9].

Analytical, diagnostic and therapeutic context of CDK5RAP1

• Co-immunoprecipitation data suggested that C42 and p35(nck5a) could form a complex within cultured mammalian cells [6].
• CONCLUSIONS: The C42 generation assay is another functional assay of serum complement which can provide information beyond that obtained from the typical serum CH50 assay [19].
• The specific human IgE antibodies against recombinant C42 from either E. coli (C42-E. coli) or COS-1 (C42-COS-1) were compared by ELISA with 12 sera from Per a 1 and C42 skin-test-positive patients [1].

References