In the pathway, NF-κB/Rel proteins are bound and inhibited by IκB proteins. Growth factors, proinflammatory cytokines, chemotherapy, radiotherapy, and antigen receptors activate an IKK complex, which phosphorylates IκB proteins. Phosphorylation of IκB leads to its ubiquitination and proteasomal degradation, freeing NF-κB/Rel complexes. The transcription factor NF-κB is thereby released and promotes the expression of cytokines, cell adhesion molecules, and antiapoptotic proteins. The NF-κB signal transduction pathway in development and dysfunction of the immune system. In NF-κB pathway, most proteins regulate the expression of genes influencing a broad range of biological processes including innate and adaptive immunity, inflammation, stress responses, B-cell development, and lymphoid organogenesis.
Nuclear factor kappa B is a dimer belonging to Rel family, that contains a highly conserved Rel-homology domain (RHD). The NFκB proteins have five different monomers that share a Rel homology domain in their N-terminus. The p105 and p100 which precursors of NFκB1 and NFκB2 that are transformed to mature NFκB subunits (p50 and p52) by the ubiquitin pathway. The nuclear translocation of NFκB, inhibitory kappa B (IκB) proteins, and DNA binding interaction with RHD.
NFκB signalling pathway have two major ways,that as : (1) the canonical (mediated by IκB degradation), and (2) the non-canonical (p100 mediated) pathways. In the cell ,the NFκB dimers are attached to IκB proteins under normal conditions. The canonical pathway will be activated by the inflammatory reaction, for example,interleukins, TNF-α, or LPS, that leads to the activation of the IκB kinase (IKK) complex. Then NFκB becomes free, which follows it moves to the nucleus and initiates transcription of the target genes.
The cell cycle is an ordered set of events, culminating in cell growth and division. The cell cycle of eukaryotes can be divided in two brief periods: interphase, during which the cell grows, accumulating nutrients needed for mitosis and duplicating its DNA, and the mitosis (M) phase, during which the cell splits itself into two distinct cells, often called "daughter cells". By studying molecular events in cells, interphase is divided into three stages, G1, S, and G2. Thus the cell cycle consists of four phases: G1, S, G2, M.
G1 phase is from the end of the previous M phase until the beginning of DNA synthesis, and G stands for gap. During this phase the biosynthetic activities of the cell, which had been considerably slowed down during M phase, resume at a high rate. This phase is marked by synthesis of various enzymes that are required in S phase, mainly those needed for DNA replication. An important cell cycle control mechanism activated during this period (G1 Checkpoint) ensures that everything is ready for DNA synthesis.
DNA replication occurs during the ensuing S (synthesis) phase. To produce two similar daughter cells, the complete DNA instructions in the cell must be duplicated. Thus, during this phase, the amount of DNA in the cell has effectively doubled.
The cell then enters the G2 (gap 2) phase, which lasts until the cell enters mitosis. During the G2 phase the cell will continue to grow and produce new proteins. At the end of this gap is another control checkpoint (G2 Checkpoint) to determine if the cell can now proceed to enter M (mitosis) and divide.
After the interphase, during which the cell grows and accumulates nutrients, the cell begins mitosis. Cell growth and protein production stop, all of the cell's energy is focused on the complex and orderly division into two similar daughter cells. As in both G1 and G2, there is a Checkpoint in the middle of mitosis (Metaphase Checkpoint) that ensures the cell is ready to complete cell division.
Nonproliferative cells in multicellular eukaryotes generally enter the quiescent G0 state from G1 and may remain quiescent for long periods of time. The G0 phase is even indefinitely for a cell that has reached an end stage of development and will no longer divide (e.g. neuron).
Early work in frog and invertebrate embryos suggested that cell cycle events are triggered by the activity of a biochemical oscillator centered on cyclin-CDK complexes. The cyclin/CDK complexes induce two processes, duplication of centrosomes and DNA during interphase, and mitosis. The roles of individual cyclins were tested by adding recombinant proteins to cyclin- biologidepleted extracts. Cyclin E supports DNA replication and centrosome duplication, cyclin A supports both of these processes and mitosis, and cyclin B supports mitosis alone. In the cell cycle, Cyclin D/CDK4, Cyclin D/CDK6, and Cyclin E/CDK2 regulate transition from G1 to S phase; Cyclin A/CDK2 is active in S phase; Cyclin B/CDK1 regulates progression from G2 to M phase.
It is widely accepted that the central cell cycle oscillator is based on cyclin/CDK complexes. However, this view of cell cycle regulation was challenged by evidence fora cyclin/CDK-independent oscillator in budding yeast. Haase SB and Reed SI. observed that oscillations of similar periodicity in cells responding to mating pheromone in the absence of G1 cyclin (Cln)- and mitotic cyclin (Clyclin B)-associated kinase activity in the budding yeast Saccharomyces cerevisiae. It is indicated that a previously unrecognized oscillator may play an integral role in regulating early cell cycle events. In addition, Orlando DA and colleagues discovered that a network of sequentially expressed transcription factors could regulate the bulk of the periodic transcription program and function as an oscillator independent of Cyclin B/CDKs.