Cyclins are eukaryotic proteins that play an active role in controlling nuclear cell division cycles [], and regulate cyclin dependent kinases (CDKs). This entry includes cyclin-H from vertebrates, mcs2 from fission yeast and Ccl1 from budding yeasts. They are cyclins that play a role in cell cycle. They are also subunits forming the core-TFIIH basal transcription factor. Human cyclin-H regulates CDK7, the catalytic subunit of the CDK-activating kinase (CAK) enzymatic complex []. mcs2 posseses kinase activity that can be detected when myelin basic protein (MBP) is provided as an exogenous substrate []. Ccl1 is a regulatory component of the TFIIK complex, which is the protein kinase component of transcription factor IIH (TFIIH). TFIIH is essential for both basal and activated transcription and is involved in nucleotide excision repair (NER) of damaged DNA and in polymerase II transcription [].
Within mitochondria and bacteria, a family of related proteins is involved in the assembly of periplasmic c-type cytochromes: these include CycK [], CcmF [, ], NrfE []and CcbS []. These proteins may play a role in guidance of apocytochromes and haem groups for their covalent linkage by the cytochrome-c-haem lyase. Members of the family are probably integral membrane proteins, with up to 16 predicted transmembrane (TM) helices.The gene products of the hel and ccl loci have been shown to be required specifically for the biogenesis of c-type cytochromes in the Gram-negative photosynthetic bacterium Rhodobacter capsulatus. The ccl locus contains two genes, ccl1 and ccl2, each of which possesses typical signal sequences to direct them to the periplasm []. Ccl1 is similar to proteins encoded by chloroplast and mitochondrial genes, suggesting analogous functions in these organelles. It is believed that the hel-encoded proteins are required for the export of haem to the periplasm, where it is subsequently ligated to the c-type apocytochromes []. The CycK and CycL proteins of Bradyrhizobium japonicum share up to 53% amino acid sequence identity with R. capsulatus proteins Cc11 and Cc12 proteins, respectively. CycK and CycL proteins, which are encoded by the cycHJKL-cluster, may form part of a cytochrome c-haem lyase complex whose active site faces the periplasm [].
Cyclins are eukaryotic proteins that play an active role in controlling nuclear cell division cycles, and regulate cyclin dependent kinases (CDKs) [].This entry represents several Cyclin families (C, L, Q, T1, T2, and H/Ccl1) and yeast RNA polymerase II holoenzyme cyclin-like subunit (also known as Ssn8/Srb11).Cyclin C can regulate both cell cycle progression and gene transcription. The Cdk8-cyclin C complex is a component of the RNA polymerase II holoenzyme [].Cyclin L is a transcriptional regulator involved in the regulation of RNA polymerase II transcription and participating in regulating the pre-mRNA splicing process [, ].Cyclin Q (also known as Cyclin M) consists of cyclin-related protein FAM58A [].Cyclin-T2 is a regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin T) complex [].Cyclin-H from vertebrates, mcs2 from fission yeast and Ccl1 from budding yeasts are cyclins that play a role in cell cycle [].Cyclin-T associates with CDK9 which are subunits of the positive-transcription elongation factor (P-TEFb) [].Ssn8/Srb11 is a component of the SRB8-11 complex (consists of SRB8, SSN2/SRB9, SSN3/SRB10 and SSN8/SRB11), which is a regulatory module of the mediator complex that is involved in regulation of basal and activated RNA polymerase II-dependent transcription [, ].
Cyclin-dependent kinase 7 (CDK7) is a serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription. It is activated by binding to a cyclin; binding to a different cyclin and phosphorylation of another kinase progresses the cell cycle. CDK7 binds cyclin-B and phosphorylates CDK1 during G2-M transition, and phosphorylates CDK2 and binds to cyclins during G1-S transition [, ]. CDK7 phosphorylates and activates p53 following DNA damage [], but CDK7 is then inactivated by p53, which arrests the cell cycle, allowing the cell to recover or undergo apoptosis []. CDK7 is also the catalytic subunit of the CDK-activating kinase (CAK) complex, which also contains cyclin-H (CCNH) and MAT1 [, ]. In turn, the CAK associates with the core-TFIIH to form the TFIIH basal transcription factor [].This entry includes CDK7 from animals, Kin28 from budding yeasts and Crk1 (also known as Mcs6) from fission yeasts. S. pombe possesses two CAKs, the nonessential Csk1 and the essential Mcs6 kinases, corresponding to the yeast Cak1 and the metazoan CDK7, respectively. Mcs6 modulates gene expression through both its CAK and CTD kinase activities []. Kin28 is the closest homologue of CDK7 from budding yeasts. It forms a complex with Ccl1 and Tfb3. This complex associate with TFIIH for transcription regulating activity, but does not display CAK activity []. Instead, Cak1, a single-subunit kinase distantly related to Cdk, catalyzes Cdk activation at both transitions of the budding yeast cell cycle [].
Chemokines (chemotactic cytokines) are a family of chemoattractant molecules. They attract leukocytes to areas of inflammation and lesions, and play a key role in leukocyte activation. Originally defined as host defense proteins, chemokines are now known to play a much broader biological role []. They have a wide range of effects in many different cell types beyond the immune system, including, for example, various cells of the central nervous system [], and endothelial cells, where they may act as either angiogenic or angiostatic factors [].The chemokine family is divided into four classes based on the number and spacing of their conserved cysteines: 2 Cys residues may be adjacent (the CC family); separated by an intervening residue (the CXC family); have only one of the first two Cys residues (C chemokines); or contain both cysteines, separated by three intervening residues (CX3C chemokines).Chemokines exert their effects by binding to rhodopsin-like G protein-coupled receptors on the surface of cells. Following interaction with their specific chemokine ligands, chemokine receptors trigger a flux in intracellular calcium ions, which cause a cellular response, including the onset of chemotaxis. There are over fifty distinct chemokines and least 18 human chemokine receptors []. Although the receptors bind only a single class of chemokines, they often bind several members of the same class with high affinity. Chemokine receptors are preferentially expressed on important functional subsets of dendritic cells, monocytes and lymphocytes, including Langerhans cells and T helper cells [, ]. Chemokines and their receptors can also be subclassified into homeostatic leukocyte homing molecules (CXCR4, CXCR5, CCR7, CCR9) versus inflammatory/inducible molecules (CXCR1, CXCR2, CXCR3, CCR1-6, CX3CR1).CC chemokine receptors are a subfamily of the chemokine receptors that specifically bind and respond to cytokines of the CC chemokine family. There are currently ten members of the CC chemokine receptor subfamily, named CCR1 to 10. The receptors receptors are found in monocytes, lymphocytes, basophils and eosinophils.This entry represents CC chemokine receptor 8 (CCR8), which it is expressed predominantly in lymphoid tissues [, ]and has also been found in glomerular podocytes []and human umbilical vein endothelial cells (HUVECs) []. CCR8 is associated with Th2 lymphocytes, which are critical for allergy, and has a role in lymphocyte activation, migration, proliferation and differentiation and in allergic diseases [, , ]. CCR8 binds to CCL1 (also known as I-309) [, ]and to CCL16 (also known as liver expressed chemokine) []. It also exhibits a high affinity for three chemokines of viral origin: vMIP-I, vMIP-II and vMCC-I.
