Nuclear transport is the method by which large molecules enter and exit the cell nucleus through nuclear pore complexes. Small molecules however do not require much regulation. This method of transport and translocation provides an understanding of various protein movement between the cytoplasm and nucleoplasm of the cell. The hundreds of nuclear transport pathways allow for the study and mechanistic view of nuclear transport’s role in the onset as well as expression of multiple diseases; breast cancer being one in particular. Various nuclear transport pathways play an important role in the progression and suppression of breast cancer tumor cells. Proteins and enzymes that propagate these pathways can lead to cell proliferation or inhibition of the invasive and metastatic behavior of breast cancer advancement. A further look at these pathways will aid in the understanding of breast cancer tumor cells. Nuclear localization sequences or NLS, is a necessary component of nuclear transport. It is an amino acid sequence that will “tag” a protein for import. By disrupting this sequence, the way a protein is imported is altered and can lead to numerous defects. Where it may localize can change the functionality of the protein. This can be seen in the case of spleen tyrosine kinase, Syk. Spleen tyrosine kinase is “a candidate tumor (metastasis) suppressor that is highly expressed in mammary epithelial cells” (Wang). Lei Wang and associates looked at two different variants of Syk;
[2] – The structure of the nuclear pore complex, The Annual Review of Biochemistry 2011, Hoelz A, Debler EW, Blobel G
Inone of these steps, after prelamin A is made in the cytoplasm, an enzyme called farnesyl transferase attaches a farnesyl functional group to its carboxyl-terminus. The farnesylated prelamin A is then transported through a nuclear pore to the interior of the nucleus. The farnesyl group allows prelamin A to attach temporarily to the nuclear rim. Once the protein is attached, it is cleaved by a protease, thereby removing the farnesyl group along with a few adjacent amino acids. Failure to remove this farnesyl group permanently affixes the protein to the nuclear rim. After cleavage by the protease, prelamin A is referred to as lamin A. Lamin A, along with lamin B and lamin C, makes up the nuclear lamina, which provides structural support to the
We have all seen the pink ribbons. They have become a national, if not international symbol for breast cancer support and awareness. Breast cancer knows neither racial boundaries nor age restrictions. Females of all ages and ethnicities can develop breast cancer and it is the leading most common cancer among women. Calling attention to this often fatal disease is important by supporting its victims, families and friends of victims, as well as raising funds for breast cancer research. Though males are not immune from developing a breast cancer, for the purposes of this paper, this paper will be limited to information relating breast cancer in females.
Breast Cancer is a type of cancer where in the breast cells growth are uncontrolled. To enhance our understanding of breast cancer, knowing how any cancer can develop is crucial. Cancer develops as a result of the alteration of the genes, or abnormal changes in the genes accountable for managing the growth of the cells and maintaining their health. In each nucleus, the genes operates as the “control room.” The cells in our bodies replace themselves through a process called cell growth in which the
Numerous anti-cancer drugs and therapeutic genes exert their effect in the nucleus. However, entry into the nucleus confronts both intra- and extra-cellular obstacles that include the plasma membrane, efflux proteins, endosomal escape, and the nuclear membrane [90]. Nuclear delivery may take place following cytosolic delivery, where cytosol-targeted carriers diffuse in the cytoplasm and make their way into the nucleus on their own, known as indirect nuclear delivery. However, this strategy results in only a small percentage of intracellular drug delivery to the nucleus. Direct or nuclei-targeted delivery employs carriers to surmount overcome different barriers and deliver drugs into the nucleus
Cancer is one of the leading causes of death worldwide as it can develop in almost any organ or tissue. Significant advances in understanding the cellular basis of cancer and the underlying biological mechanisms of tumour has been vastly improved in the recent years (Jiang et al. 1994). Cancer is a genetic disease which requires a series of mutation during mitosis to develop, its characteristics can be associated with their ability to grow and divide abnormal cells uncontrollable while in the mean time invade and cause nearby blood vessels to serve its need. Even though many people are affected by cancer today, the abilities which cancer cells have make it hard to find a single effective treatment for cancer. The focus of research now lies
There are different type of nuclear receptors, types (I-IV). Steroid hormone receptors such as the estrogen receptor is type I. Type I undergoes nuclear translocation from cytoplasm into the nucleus upon ligand activation (hormone-receptor complex). The Hormone diffuses through the cell membrane where it binds to the nuclear receptor/heat shock protein in the cytosol. Upon the hormone binding, the heat shock protein dissociates. Dimerization then takes place resulting in two homodimers where it trans-locates into the nucleus, binding to inverted repeat DNA half sites called Hormone Response Elements (HREs), found within a promotor of a gene. In the case of oestrogen, it binds to oestrogen response elements. The nuclear receptor/ DNA complex
The study enables us to understand the role of the GTP-bound Ran/TC4 in the process of importing proteins into the nucleus. Therefore, this study is educative and relevant. Moreover, this Ran/TC4-GTP can also be used for cloning RanPBI cDNAs (Matsumoto & Beach, 1991). The RanPBI works closely with Ran that have been charged with GTP plays a significant role in the binding of the RNA (Matsumoto & Beach, 1991). From the above discussion and experiments conducted, we can conclude that Ran/TC4 is very vital in the importation of protein, cell cycle and in the synthesizing of DNA. This study is significant to physicians and medics who are looking for better solutions in case patients’ cells are
In the 21st century human cloning has become a huge component of modern day society, it’s mainly being looked at as a way for human infertility problems to be solved through a process of somatic cell nuclear transfer. But is this process actually helping or benefiting the cloning of humans? The answer is simple, no. Somatic cell nuclear transfer is a technique for cloning in which the nucleus is removed from a healthy egg. This egg becomes the host for a nucleus that is transplanted from another cell, such as a skin cell. The resulting embryo can be used to generate embryonic stem cells with a genetic match to the nucleus donor (therapeutic cloning), or can be implanted into a surrogate mother to create a cloned individual, such as Dolly the
The authors found that there was some variability in the expression and the splicing patterns of signaling molecules. From this variability, the authors focus on the Receptor tyrosine kinases (RTKs) because they are an important signaling molecules and is target for possible therapeutics. This variability could be a source for why some therapeutics that target RTKs are unsuccessful.
There are many organisms that use RNA (ribonucleic acid) interference, also known as RNAi to control genes, scientists can also use RNA interference as a tool in the laboratory and in the future may be able to use it as a therapy. RNA interference is described as the biological process in which RNA molecules prevent gene expression. Eukaryotic cells have many ways of controlling gene expression, as in the complex environment in a cell these mechanisms need to be precisely targeted. Small RNA molecules are used to direct gene silencing (or gene knockdown), this is called RNAi. Gene knockdown can be described as the technique used to reduce the organisms genes, this can occur through either genetic modification or treatment with a reagent
As seen in these tumors, it is clear that c-src can be involved with cancer. It had been observed on several occasions that in abnormal tissues as well as cancer cells the level the c-src protein as well as kinase are elevated and furthermore that these levels continue to increase as the level of disease progresses. There was a clear correlation between c-src activity and cancer development. In breast cancer, they found that the c-Src when overexpressed is activated by HER1 interactions and this is what causes the high kinase activity in the cancer cells. As
More than 60 Rab GTPases have been found, and they each have a particular function in vesicular transport in a cell (Hutagalung and Novick, 2011). For example, Rab 27a and Rab27b are of particular interest in melanoma due to their function of melanosome transport. (Figure 5) Rab27a has been identified as a tumour dependency gene in melanoma (Akavia et al., 2010).
However, it is not necessarily always associated with metastasis, as only 0.01% of CTCs takes part in metastasis92, 94, 95. Moreover, highly sensitive, single cell investigation showed marked heterogeneity of individual CTCs for protein expression and localization, and the CTCs reflected the character of both the primary biopsy and the transformations seen in the metastatic sites96, 97, which corresponds with the evidence of “seed and soil” hypothesis98-100.
We noted that the K59R mutation of IRF4 is in a highly conserved region of the DNA binding domain. We hypothesized that this might affect protein levels, localization, or transcriptional activation potency. We observed increased nuclear expression of K59R mutant IRF4 as compared to wild-type protein, without changes in cytosolic levels. This difference was not affected by proteasome or nuclear export inhibitors suggesting that differences in degradation or nuclear export do not cause the observed differences in nuclear levels. This suggests that the difference in nuclear levels may be due to differences in import or sequestration by other nuclear localized molecules.