Transcription nuclear membrane

Fig. 5.1 Regulators of pre- and post-integration latency. Pre-integration latency is regulated as the viral RNA is reverse transcribed into the proviral DNA (A). This is controlled by the avaUabdity of the nucleotide pool, half life of the forming proviral cDNA copy, and the interaction of the viral protein Vif with the cellular antiviral protein APOBEC, espedaUy family members 3G and 3R It is also regulated at the step of transport across the nuclear membrane through the availability of ATP as the process requires energy (B). Post-integration, the proviral DNA copy of the viral genome, is regulated maiiily by the avadabdity of host transcription factors, especially NF-kB and NFAT (C)...

The protein synthesis machinery reads the RNA template starting from the 5 end (the end made first) and makes proteins beginning with the amino terminus. These directionalities are set up so that in prokaryotes, protein synthesis can begin even before the RNA synthesis is complete. Simultaneous transcription-translation can t happen in eukaryotic cells because the nuclear membrane separates the ribosome from the nucleus. 

Entry of animal cells into mitosis is based on the mitosis-promoting factor (MPF). MPF consists of CDK1 (cdc2) and cyclin B. The intracellular concentration of cyclin B increases constantly until mitosis starts, and then declines again rapidly (top left). MPF is initially inactive, because CDKl is phosphorylated and cyclin B is dephosphorylated (top center). The M phase is triggered when a protein phosphatase [1] dephosphorylates the CDK while cyclin B is phosphorylated by a kinase [2]. in its active form, MPF phosphorylates various proteins that have functions in mitosis—e.g., histone HI (see p. 238), components of the cytoskeleton such as the laminins in the nuclear membrane, transcription factors, mitotic spindle proteins, and various enzymes. 

Spindle formation Chromosome condensation Disappearance of nuclear membrane Transcription stop Cyclin degradation... 

In M phase, new phosphorylation of many proteins is observed that starts, in particular, from the CDC2-cyclin B complex. The phosphorylation mostly affects proteins involved in the reorganization of the cytoskeleton, the nuclear membrane and the formation of the spindle apparatus. As a consequence of phosphorylation events, inhibition of vesicular transport and general inhibition of transcription occur. 

Eukaryotic cells have six general types of signaling mechanisms gated ion channels receptor enzymes membrane proteins that act through G proteins nuclear proteins that bind steroids and act as transcription factors membrane proteins that attract and activate soluble protein kinases and adhesion receptors that carry information between the extracellular matrix and the cytoslceleton. 

The absence of a nuclear membrane is a characteristic of bacteria that has a profound effect on transcription. Bacterial transcripts are processed rapidly, and their 5 ends often enter ribosomes and are directing protein synthesis, while the 3 ends of the genes are still being transcribed. In contrast, most eukaryotic RNA transcripts must be processed and transported out of the nucleus before they can function. As consequence, many aspects of the control of transcription differ between prokaryotes and eukaryotes. 

We have stated that translation begins before transcription is completed in prokaryotes. The situation is quite different in eukaryotes, where transcription and translation occur in different cellular compartments separated by the nuclear membrane. Large precursors of mRNA are synthesized in the nucleus these become complexed with proteins to form ribonucleoprotein particles which are modified and processed to form smaller mRNAs that become transported across the nuclear membrane to the cytoplasm. 

It is apparent from the above discussion that Ki-67 is present in the nucleus of proliferating cells and is an indicator of the growth fraction in tumor cells. It is primarily a DNA-binding protein that plays a crucial role in the maintenance or regulation of cell division. This protein may also function as a matrix for chromosomal DNA or contribute to the condensation of the chromosomes or be involved in breakdown of the nuclear membrane before mitosis (Duchrow et al., 1994). The association of Ki-67 with RNA in the nucleoli and with the DNA with nuclear matrix suggests that the antigen plays a role in transcriptional processes as a structural protein by mediating between nuclear DNA and nucleolar RNA. 

Figure 12.1 Cellular barriers to gene delivery. Extracellular DNA, delivered to cells in either viral particles, liposomes, or other vehicles, must traverse the plasma, endosomal, and nuclear membranes before any transcription, replication, or integration can occur.

Serine proteases, released from immune cell granules, process cytokines and growth factors that control multiple cellular process [56], Proteinase 3, cathepsin G, and elastase all cleave membrane-bound TNF-o, IL-1, and IL-18, and activate epidermal growth factor receptor (EGFR) and toll-like receptor-4 (TLR-4). These actions inhibit growth and lead to apoptosis with transcriptional nuclear factor kB (NF-kB) inactivation. Bik suppresses release of TNF-o, IL-1, and IL-18 and prevents EGFR and TLR-4 activation. Activation of NF-kB is a mediator of cell proliferation, whereas inhibition of NF-/. B leads to apoptosis [82]. Overall, Bik inhibition of immune cell serine proteases increases cell proliferation and stability. 

Trioidothyronine from plasma, or that generated from T4 in the cells, may interact with specific cell receptors. However, there seems to be an equilibrium between the free and bound T3, and T3 penetrates the nuclear membrane without being bound to the cytoplasmic receptor protein. In the nucleus, however, T3 interacts with a chromatin-bound receptor and affects mRNA transcription. The responsiveness of various cells to T3 is correlated with the presence of nuclear T3 receptors. T3 receptors are also present in mitochondria 02 consumption by mitochondria is increased under the influence of T3. The function of cytosolic T3 receptors may be simply to concentrate T3 inside the cell rather than to serve as transporters. These processes are illustrated in Figure 16.15. 

Eukaryotes potentially have many more opportunities for control of gene expression than do bacteria. For example, the cell could take advantage of control at the level of the processing of primary transcripts. It is known that RNA is not transported across the nuclear membrane until all introns are excised. A more subtle form of control could involve alternative modes of splicing a particular transcript. There are now examples known where this occurs to yield different mRNA molecules. Perhaps one of the best-known examples of yet another level of control in eukaryotes is that of translational control of globin synthesis. 

Most transcripts must be processed before becoming fully functional. Most eukaryotic RNA must be transported across the nuclear membrane where it is processed then transported to the cytosol. Processing helps stabilize and protect the RNA so it can function in the cytosol and also functions in regulating the expression of certain genes. 

The steroid molecule is hydrophobic and is able to diffuse through the cell membrane and finds its receptor waiting for it in the cytoplasm of the cell. Receptor and steroid combine and the complex travels across the nuclear membrane into the nucleus whereupon it binds (still as the receptor/steroid complex) to an acceptor site on the cell s DNA. This binding then switches on transcription and the synthesis of mRNA. 

The nuclear membrane. In eukaryotes, transcription and translatio i take place in different cellular compartments transcription takes place in the membrane-bounded nucleus, whereas translation takes place outside the nucleus in the cytoplasm. In prokaryotes, the two processes are closely coupled Figure 29.15). Indeed, the translation of bacterial mRNA begins while... 

---