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PubMed2004

Accurate mass measurement and tandem mass spectrometry of intact globin chains identify the low proportion variant hemoglobin Lepore-Boston-Washington from the blood of a heterozygote.

Within a mixture of proteins, minor polymorphic components are difficult to identify using a conventional proteomic approach. Their identification generally requires multi-dimensional separation steps, before or after proteolytic cleavage, followed by sequence analysis of the proteolytic products. In this study, we investigated the potential of tandem mass spectrometry for protein characterization by identifying the delta-beta hybrid human hemoglobin variant Lepore-Boston-Washington using electrospray ionization tandem mass spectrometry. Hemoglobin Lepore-Boston-Washington occurs mainly in heterozygotes, where it comprises approximately 10% of the total non-alpha-chains, the dominant non-alpha-chain being the normal beta (approximately 90%). Furthermore, Hemoglobin Lepore-Boston-Washington has an average molecular mass (15,865.23 Da) that is only 2 Da lower than that of the normal beta-chain (15,867.24 Da). Consequently, it cannot be resolved from the normal beta-chain by mass spectrometry. Here we show how Hemoglobin Lepore-Boston-Washington was identified directly from the diluted blood of a heterozygote by analyzing the product ions from the Lepore-Boston-Washington and normal beta-chain ions without prior separation of the individual chains. This study shows the potential of the tandem mass spectrometry for identifying a minor component in an unseparated mixture of proteins.

Amino Acid Sequence↗
PubMed2003

The Delta Np63 alpha phosphoprotein binds the p21 and 14-3-3 sigma promoters in vivo and has transcriptional repressor activity that is reduced by Hay-Wells syndrome-derived mutations.

p63 is a recently identified homolog of p53 that is found in the basal layer of several stratified epithelial tissues such as the epidermis, oral mucosa, prostate, and urogenital tract. Studies with p63(-/-) mice and analysis of several human autosomal-dominant disorders with germ line p63 mutations suggest p63 involvement in maintaining epidermal stem cell populations. The p63 gene encodes six splice variants with reported transactivating or dominant-negative activities. The goals of the current study were to determine the splice variants that are expressed in primary human epidermal keratinocytes (HEKs) and the biochemical activity p63 has in these epithelial cell populations. We found that the predominant splice variant expressed in HEKs was Delta Np63 alpha, and it was present as a phosphorylated protein. During HEK differentiation, Delta Np63 alpha and p53 levels decreased, while expression of p53 target genes p21 and 14-3-3 sigma increased. Delta Np63 alpha had transcriptional repressor activity in vitro, and this activity was reduced in Delta Np63 alpha proteins containing point mutations, corresponding to those found in patients with Hay-Wells syndrome. Further, we show that Delta Np63 alpha and p53 can bind the p21 and 14-3-3 sigma promoters in vitro and in vivo, with decreased binding of p63 to these promoters during HEK differentiation. These data suggest that Delta Np63 alpha acts as a transcriptional repressor at select growth regulatory gene promoters in HEKs, and this repression likely plays an important role in the proliferative capacity of basal keratinocytes.

14-3-3 Proteins↗
PubMed1989

T-cell antigen receptor (TCR)-alpha/beta heterodimer formation is a prerequisite for association of CD3-zeta 2 into functionally competent TCR.CD3 complexes.

In order to study the relationship between assembly, surface expression, and signal transduction of the alpha/beta T-cell antigen receptor-CD3 complex (TCR.CD3), a series of T-cell mutants with a partial block in assembly of the complex was generated. By chemical mutagenesis, we produced somatic cell variants of the human T-leukemia cell line, HPB-ALL, which expressed low amounts of TCR.CD3 complexes on their surface. RNA and protein analyses demonstrated that most variants synthesized normal amounts of the individual members of the complex, i.e. TCR-alpha, TCR-beta, CD3-gamma, -delta, -epsilon, and -zeta. In these variants, less than 10% of the TCR.CD3 complexes inside the cell contained the CD3-zeta 2 homodimer due to an intrinsic deficiency in the formation of the TCR-alpha/beta heterodimer. The low level of assembly of CD3-zeta 2 into the TCR.CD3 complex and an additional decrease in the rate of export of the TCR.CD3 complex from the endoplasmic reticulum explained the low level of expression of alpha/beta receptors on the surface of these mutants. Only cells with the complete set of subunits of the TCR.CD3 complex on their surface were capable of transducing CD3-mediated signals. The results presented in this paper indicate that TCR-alpha/beta heterodimer formation is an obligatory requirement for assemblage of CD3-zeta 2 into a functionally competent TCR.CD3 complex.

Antigens, CD↗
PubMed1999

Structure/function analysis of human cystatin SN and comparison of the cysteine proteinase inhibitory profiles of human cystatins C and SN.

Cystatins are reversible, competitive inhibitors of cysteine proteinases. Their inhibitory profiles, as well as their affinities for target enzymes, vary with different cysteine proteinases. Human cystatin C and salivary cystatin SN are 120- and 121-amino-acid (a.a.) proteins, respectively, and both contain 2 disulfide bonds. In this study, we examined the structure/function relationship of cystatin SN with respect to the inhibition of papain, with particular emphasis on the role of cystatin SN's cysteine residues, and addressed the inhibitory profiles of these two human cystatins on several cysteine proteinases (papain, clostripain, and calpain II). The full-length recombinant cystatin C and cystatin SN, and cystatin SN variants (C-truncated [C-tr; a.a. 1-102], delta 56-60 deletion, cysteine 74-->serine [C74S], cys 84-->serine [C84S], cysteine 98-->serine [C98S], and cysteine 118-->serine [C118S]) were cloned, expressed, and produced in the pET30(b) and pGEX2T Escherichia coli expression systems. All recombinant proteins were tested for the inhibition of papain, and the full-length proteins were also tested for the inhibition of clostripain and calpain II. The secondary structures of the cystatins were also determined and compared. The results showed that the full-length cystatin C and cystatin SN, and the cystatin SN variants C98S and C118S inhibited the activity of papain. However, cystatin SN C-tr and delta 56-60 variants exhibited no inhibitory activity toward papain, while the cystatin SN variants C74S and C84S exhibited slight inhibition at higher concentrations. These results suggested that in the inhibition of papain by cystatin SN, the first disulfide loop is more important than the second. In addition, cystatin C, but not cystatin SN, inhibited calpain II, while neither cystatin inhibited clostripain, and these results, in conjunction with those from other studies, indicated that cystatin C is a broader-spectrum inhibitor of cysteine proteinases than cystatin SN.

Calpain↗
PubMed1992

Comparison of the biological and immunological properties of glycosylation deficient human chorionic gonadotropin variants produced by site directed mutagenesis and chemical deglycosylation.

Appropriate glycosylation of gonadotropins is essential for the full expression of their biological activity. In this investigation we have compared the properties of glycosylation deficient human chorionic gonadotropin (hCG) produced by chemical deglycosylation (HF treatment--DG-hCG) or recombinant techniques (site directed mutagenesis). Among the recombinant hCG molecules secreted into the culture medium, the following variants containing selective N-glycosylation deletions at delta alpha 1 or delta alpha 1,2 or in both subunits could not stimulate steroidogenesis in mouse Leydig tumor cells (MA-10 cell line) and in this respect were very similar to DG-hCG. The other variants were fully active like native hCG, but the alpha + delta beta 1,2 recombinant hCG was a partial agonist. In radioimmunoassay with antibodies against native hCG, the DG-hCG as well as all recombinant hCG variants, including the wild type (WT), were similar. However, with antisera against DG-hCG or affinity purified antibodies specific to DG-hCG the alpha/delta 1,2 beta mutant, the WT hormone and native hCG were less active. In this assay mutants containing N-glycosylation deletions in the alpha subunit as well as the delta alpha 1,2/delta beta 1,2, variant showed higher activity. A similar pattern was evident in reaction with a selected monoclonal antibody showing preferential binding of 125I-labeled DG-hCG (antagonist). Affinity purified antibody directed against native hCG conformation was successful in converting DG-hCG and some inactive glycosylation deficient variants into an active form by stimulating progesterone in MA-10 cells. These data suggest that there are similarities as well as subtle differences in conformation of DG-hCG and various recombinant hCG molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Amino acid sequence of an alpha-delta-glycophorin hybrid. A structure reciprocal to Sta delta-alpha-glycophorin hybrid.

In this report we examine the primary sequence of a variant glycophorin obtained from erythrocytes of an individual who exhibits an unusual MNSs blood group phenotype. We show that this protein is a hybrid molecule constructed from sequences of alpha- and delta-glycophorins (glycophorins A and B) in a alpha-delta arrangement. Serological typing revealed that the donor's phenotype was M+N+S+s+U+; yet his erythrocytes reacted with some but not all examples of anti-S antisera. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed a variant glycophorin band, and immunoblotting and reaction with N-glycanase suggested that its amino terminus resembled that of M-alpha-glycophorin but that its carboxyl terminus did not. A preparation highly enriched in the variant was obtained and used to generate peptide fragments for sequencing. The sequence revealed that the variant was a hybrid molecule whose amino terminus corresponded to M-alpha-glycophorin and whose carboxyl terminus corresponded to S-delta-glycophorin. CNBr cleavage of the variant glycophorin yielded four peptides. The sequence of the amino-terminal CNBr peptide (residues 1-8) was identical to the amino-terminal octapeptide of M-alpha-glycophorin. The proceeding peptide (residues 9-61) contained a segment identical to residues 9-58 of alpha glycophorin, but its carboxyl-terminal sequence had the Gly-Glu-Met sequence from S-delta-glycophorin (residues 27-29). The other two peptides, insoluble in aqueous solutions, contained highly hydrophobic sequences, identical to residues 30-52 and 53-68 of delta-glycophorin. Sequences of overlapping peptides generated by trypsin and V8 protease confirmed the hybrid nature of the variant glycophorin: residues 1-58 were identical to residues 1-58 of M-alpha-glycophorin, and residues 59-100 were entirely identical to residues 27-68 of S-delta-glycophorin. The variant glycophorin is expected to have 4 additional residues at its carboxyl terminus that correspond to the carboxyl-terminal residues 69-72 of delta-glycophorin. The amino acid sequence arrangement of the variant alpha-delta-glycophorin is an exact reciprocal of that found in another hybrid glycophorin, Sta, that is a delta-alpha hybrid. We propose that the two hybrid glycophorins represent the two possible products resulting from a reciprocal recombination event.

Amino Acid Sequence↗
PubMed2002

Molecular cloning and characterization of the human voltage-gated calcium channel alpha(2)delta-4 subunit.

The voltage-gated calcium channel is composed of a pore-forming alpha(1) subunit and several regulatory subunits: alpha(2)delta, beta, and gamma. We report here the identification of a novel alpha(2)delta subunit, alpha(2)delta-4, from the expressed sequence tag database followed by its cloning and characterization. The novel alpha(2)delta-4 subunit gene contains 39 exons spanning about 130 kilobases and is co-localized with the CHCNA1C gene (alpha(1C) subunit) on human chromosome 12p13.3. Alternative splicing of the alpha(2)delta-4 gene gives rise to four potential variants, a through d. The open reading frame of human alpha(2)delta-4a is composed of 3363 base pairs encoding a protein with 1120 residues and a calculated molecular mass of 126 kDa. The alpha(2)delta-4a subunit shares 30, 32, and 61% identity with the human calcium channel alpha(2)delta-1, alpha(2)delta-2, and alpha(2)delta-3 subunits, respectively. Primary sequence comparison suggests that alpha(2)delta-4 lacks the gabapentin binding motifs characterized for alpha(2)delta-1 and alpha(2)delta-2; this was confirmed by a [(3)H]gabapentin-binding assay. In human embryonic kidney 293 cells, the alpha(2)delta-4 subunit associated with Ca(V)1.2 and beta(3) subunits and significantly increased Ca(V)1.2/beta(3)-mediated Ca(2+) influx. Immunohistochemical study revealed that the alpha(2)delta-4 subunit has limited distribution in special cell types of the pituitary, adrenal gland, colon, and fetal liver. Whether the alpha(2)delta-4 subunit plays a distinct physiological role in select endocrine tissues remains to be demonstrated.

Acetates↗
PubMed2005

Molecular and clinical epidemiology of CXCR4-using HIV-1 in a large population of antiretroviral-naive individuals.

OBJECTIVE: We wished to characterize the epidemiological and clinical correlates of CXCR4-using human immunodeficiency virus type 1 (HIV-1) ("X4 variants") in a cross-sectional analysis of a large population of antiretroviral-naive individuals. METHODS: HIV-1 coreceptor use was determined in the last pretherapy plasma sample for 1191 individuals initiating triple-combination therapy in British Columbia, Canada. Baseline variables investigated included sociodemographic characteristics, plasma viral load (pVL), CD4 cell count, AIDS diagnosis, HIV-1 V3 loop sequence, and human CCR5 Delta 32 genotype. RESULTS: Individuals harboring X4 variants (n = 178 of 979 phenotyped samples; 18.2%) displayed a poorer baseline clinical profile than individuals harboring exclusively CCR5-using HIV-1 ("R5 variants") (median pVL, 175,000 vs. 120,000 copies of HIV-1 RNA/mL [P = .0006]; median CD4 cell count, 110 vs. 290 cells/mm(3) [P < .0001]). Individuals heterozygous for the CCR5 Delta 32 deletion (n = 128 of 967; 13.2%) were at 2.5 times higher risk of harboring X4 variants, compared with those without the deletion (multivariate P = .0005). The presence of basic amino acids at codon 11 and/or codon 25 of HIV-1 V3 (n = 109 of 955; 11.4%) was associated with a 9.1 times higher risk of harboring X4 variants (multivariate P < .0001), regardless of CCR5 Delta 32 genotype. In multivariate analyses adjusting for baseline parameters, HIV-1 coreceptor use was not found to be a significant predictor of survival or treatment response. CONCLUSION: Baseline CD4 cell count, pVL, HIV-1 V3 sequence, and CCR5 Delta 32 genotype were the strongest determinants of CXCR4-using HIV-1 in this population. After adjustment for baseline parameters, the presence of X4 variants before initiation of highly active antiretroviral therapy was not independently associated with a poorer outcome of therapy.

Adult↗
PubMed1996

Expression studies of delta-globin gene alleles associated with reduced hemoglobin A2 levels in Greek Cypriots.

We previously identified five delta-globin gene alleles associated with reduced hemoglobin (Hb) A2 (Trifillis, P., Ioannou, P., Schwartz, E., and Surrey, S. (1991) Blood 78, 3298-3305). We have now evaluated functional consequences of the changes after expression in COS-1 cells to monitor effects on RNA splicing. In addition, variant Hb A2 tetramers were expressed in yeast to assess effects of amino acid changes on oxygen binding and stability to heat and mechanical agitation. The G --> T change at codon 27 and the A --> G change in IVS-2 both affect RNA splicing, whereas the C --> T change at codon 97 and the AT deletion in IVS-2 have no effect. Oxygen equilibrium curves of the Hb A2 variants expressed in yeast were similar to that of wild type Hb A2. None of the three variant Hb A2 tetramers (Thr --> Ile at codon 4 (Hb deltaT4I), Ala --> Ser at codon 27 (Hb deltaA27S), and Arg --> Cys at codon 116 (Hb deltaR116C)) showed decreased heat stability compared with Hb A2, whereas the Hb deltaT4I variant showed highest instability to mechanical agitation. Co-expression in yeast of alpha-globin chain and the delta-chain variant containing a Leu --> Pro change at codon 141 yielded no identifiable tetramers, suggesting lack of assembly or severe tetramer instability. These studies show the probable cause for decreased Hb A2 for two alleles is due to defective splicing, whereas decreased protein stability, increased tetramer association with red cell membranes, increased interdisulfide bond formation of delta-chains, which inhibits assembly with alpha-chains, and/or reduced assembly is suggested for the other three alleles.

Alleles↗
PubMed1995

Molecular characterisation of the glucose-6-phosphate dehydrogenase (G6PD) Ferrara II variant.

During the last ten years, molecular biological techniques such as cloning and sequencing and, more recently, polymerase chain reaction (PCR) amplification have led to the identification of the molecular defects responsible for more than fifty glucose-6-phosphate dehydrogenase (G6PD) variants. In this paper, we report the identification of the molecular abnormality underlying the G6PD Ferrara II variant, present in the Po delta area of Northern Italy. Biochemical characterisation shows an enzymatic activity of about 15% of normal (WHO class III), slow electrophoretic mobility, low Km for G6P, high percentage substrate analogue utilisation and a biphasic pH optimum curve. After PCR amplification, non-radioisotopic single-strand conformation polymorphism analysis carried out for the entire coding region has revealed a mobility shift in exon 8. Nucleotide sequencing has demonstrated a missense 844 G > C mutation, causing an Asp > His amino-acid replacement, known as being responsible for G6PD Seattle, G6PD Modena and G6PD Lodi.

Adult↗
PubMed1987

Cloning and nucleotide sequence of different iso-IS231 elements and their structural association with the Tn4430 transposon in Bacillus thuringiensis.

A family of five repetitive sequences (RS) has been isolated from a plasmid DNA library of Bacillus thuringiensis strain berliner 1715. In a previous paper [Mahillon et al., EMBO J. 4(1985)3895-3899] one of these was shown to harbor all the features of an IS element (IS231). Further nucleotide sequence analysis revealed that two other RS, flanking the delta-endotoxin gene, are actually variants of IS231. Comparison of the nucleotide sequences surrounding the iso-IS231 elements showed a unique structural association between some of these elements and the transposon Tn4430. Although these IS231 elements have transposed into Tn4430, both these IS231 s and the transposon Tn4430 remain structurally intact.

Bacillus thuringiensis↗
PubMed2006

Laser ablation condensation, coalescence, and phase change of dense gamma-Al(2)O(3) particles.

Dense gamma-Al(2)O(3)condensates, with residual stress up to 3 GPa and ranging from nanometer to an unexpected micrometer size, were formed by pulsed laser ablation on Al target under oxygen background gas for a very rapid heating and cooling effect. Analytical electron microscopic observations indicated such nanoparticles tended to coalesce over {111} facets to form multiple twin and tilt boundary. The micrometer-size particles changed, upon electron irradiation, into metastable orthorhombic delta form full of twin variants and faults parallel to {100}.

Journal Article↗
PubMed2001

Role and identification of protein kinase A anchoring proteins in vasopressin-mediated aquaporin-2 translocation.

The antidiuretic hormone arginine vasopressin (AVP) regulates water reabsorption in renal principal cells by inducing a cAMP/protein kinase A-dependent translocation of water channels [aquaporin-2 (AQP2)] from intracellular vesicles into the apical cell membranes. Using primary cultured rat inner medullary collecting duct (IMCD) cells, it has been shown that AQP2 translocation in response to AVP stimulation occurs only if protein kinase A (PKA) is anchored to PKA anchoring proteins (AKAPs), which are present in various subcellular compartments. The identity of the AKAPs involved has not yet been elucidated. One potential candidate is a new splice variant of AKAP18, namely AKAP18 delta.

A Kinase Anchor Proteins↗
PubMed2005

Brownian motion in an aging medium.

The motion of a particle in an aging medium can be described by the generalized Langevin equation, in the limit of long waiting time t(w) where the medium is in a quasistationary regime at the scale of the observation times investigated (t<< t(w) ) . In this framework, we analyze the link between the Brownian motion and the effective temperature which characterizes the out-of-equilibrium properties of the medium. This effective temperature involves a frequency-dependent effective temperature T(eff) (omega) formally identical to a generalized susceptibility. The analytical results are reported in the case when T(eff) (omega) is mapped to the universal non-Debye power-law ac response met for instance in dielectrics. In the particular case where the viscous friction coefficient is a power law gamma (omega) proportional, variant mid R:omegamid R:(delta-1) , contact is made with the heuristic expression T(eff) =T [1+ (omega/ omega(0) )(alpha) ] , postulated in prior experimental and theoretical works. A closed analytic form of the time correlation function of the medium coordinate (the noise force) C(FF) (t- t(') ) = F (t) F ( t(') ) is obtained, in the subdiffusive regime (delta<1) where C(FF) (t- t(') ) is a regular function. This time correlation is long range. We also determine another effective temperature T(')(eff) (t- t(') ) of the medium, usually defined in aging systems as the temperature associated with the violation of the fluctuation-dissipation theorem in its time formulation. This temperature takes the form T(')(eff) (t- t(') ) =T [1+ ( mid R:t- t(') mid R: / t(0) )(-alpha) ] >T . The results are discussed and compared with experiments.

Journal Article↗
PubMed1980

New clinical and biochemical findings from 235 patients with hemoglobin Lepore.

The study of 76 Leporian families with 214 heterozygous, 9 homozygous, and 12 combinations with different type of thalassemia has allowed the authors to discuss three points: (1) The homozygous condition for Hb Lepore was until now found only in 19 people worldwide. The affirmation that this state is always similar to classic Cooley's anemia cannot be confirmed by us because the majority of our patients did not have a very severe anemia and they are still alive and in a fairly good condition. Splenectomy is always useful. In two of our patients it was found that the ratios between delta + beta and alpha mRNA agreed well with the delta beta/alpha chain biosynthetic ratio. (2) Two new forms of combined Leporian conditions were investigated. These are the combinations of Hb Lepore with delta beta thalassemia and a variant of beta thalassemia, namely, the isolated-high-Hb-A2 beta thalassemia. Both diseases present the same Hb pattern as that of homozygous Hb Lepore. Both presented a mild course also. (3) The multiform and very large experience (more than 5000 cases of genotypical hemoglobinopathies observed in the last 20 years) led us to observe that in carriers of Hb Lepore there was frequently the concomitance of malignancies, especially hemolymphoblastoses. In fact, the risk of such malignancies in the Hb Lepore carriers is 10 times higher than for thalassemics. The explanation of this finding is uncertain. It is possible, however, that the peculiar abnormality of Hb Lepore may be related to malignancy.

Adult↗
PubMed1980

Cannabinoid compounds in South African Cannabis sativa L.

Dagga (Cannabis sativa L.) samples were collected from various geographical regions of South Africa. These were classified into age, sex and plant part and the cannabinoids were analysed quantitatively by gas-liquid chromatography and mass spectrometry. Analytical results show that there appears to be at least three chemovariants of Cannabis sativa growing in South Africa with respect to relative cannabinoid content. One of these variants appears to be unique to Southern Africa. It also appears that South African C. sativa ranks among the world's more potent C. sativa variants in terms of its delta 9-tetrahydrocannabinol content.

Cannabinoids↗
PubMed2000

Nectin2alpha (PRR2alpha or HveB) and nectin2delta are low-efficiency mediators for entry of herpes simplex virus mutants carrying the Leu25Pro substitution in glycoprotein D.

The receptors for entry of herpes simplex viruses 1 and 2 (HSV-1 and -2), widely expressed in human cell lines, are members of a subset of the immunoglobulin superfamily exemplified by herpesvirus entry mediator C (HveC) and the herpesvirus immunoglobulin-like receptor (HIgR). This report focuses on two members of this subset, herpesvirus entry mediator B (HveB), recently designated nectin2/PRR2alpha, and its splice variant isoform, nectin2/PRR2delta. Nectin2alpha and -delta share the ectodomain but differ in the transmembrane and cytoplasmic regions. HveB was reported to enable entry of HSV-1 carrying mutations in glycoprotein D (gD) and of HSV-2, but not of wild-type (wt) HSV-1. We report that (i) both nectin2alpha and -delta served as receptors for the entry of HSV-1 mutant viruses HSV-1(U10) and -(U21) and AP7(r) that carry the Leu25Pro substitution in gD but not for HSV-1 mutants U30 and R5000 that carry the Ser140 or Ala185 substitution in gD. All of these mutants were able to overcome the block to entry mediated by expression of wt gD. (ii) Infection of cells expressing nectin2alpha or -delta required exposure to multiplicities of infection about 100-fold higher than those required to infect cells expressing HveC or HIgR. (iii) gD from HSV-1(U21) bound in vitro soluble forms of nectin2. The association was weaker than that to the soluble form of HveC/HIgR. Binding of wt HSV-1 gD to soluble nectin2 was not detectable. (iv) A major region of nectin2 functional in virus entry mapped to the V domain, located at the N terminus.

Amino Acid Substitution↗
PubMed2005

The role of the casein kinase 1 (CK1) family in different signaling pathways linked to cancer development.

The members of the casein kinase 1 (CK1) family are highly conserved and are expressed in many eukaryotes ranging from yeast to humans. Mammalian CK1 isoforms (alpha, beta, gamma, delta, epsilon) and their splice variants are involved in diverse cellular processes including membrane trafficking, circadian rhythm, cell cycle progression, chromosome segregation, apoptosis and cellular differentiation. Mutations and deregulation of CK1 expression and activity has been linked to various diseases including neurodegenerative disorders such as Alzheimer's and Parkinson's disease, sleeping disorders and proliferative diseases such as cancer. In this review, we summarize the functions of CK1 and outline the participation of CK1 in signal transduction pathways linked to cancer development.

Animals↗