Share this post on:

in the resistance of pancreatic cancer cells to treatment with gemcitabine. Moreover, SRSF1 overexpression has been related to expression of two isoforms of the BCL-2 family proapoptotic BIM, BIM 1 and BIM 2. As they both lack the BH3 domain and the C-terminal hydrophobic regions, proapoptotic functions cannot be performed. Increased SRSF1 phosphorylation induced by hyperactivation of AKT can also result in the production of CASP9 prosurvival isoforms in nonsmall cell lung cancers. In addition, SRFS1 along with the protein SAM68 regulates the expression of the cyclin D1 isoform CD1b which is involved in cell transformation. As previously mentioned, SRSF1 has also been found to play a crucial role in angiogenesis since its knockdown prevents angiogenesis and tumor growth. Regardless of the examples herein cited, readers may find 4. Splicing Regulatory Kinases and Their Roles in Cancer A diverse number of kinases have been reported to transfer phosphate groups to SR proteins. In the next sections, the main players of this context will be analyzed, that is, Serinearginine Protein Kinases and CDC-like kinases, both responsible for phosphorylating SR proteins in vivo. 4.1. SRPKs. The SRPKs are serine/threonine kinases that specifically recognize and phosphorylate SR proteins at Ser/Arg dipeptide in a processive manner. Until now, four members of this protein family have been described in mammalian cells, that is, SRPK1, SRPK1a, SRPK2, and SRPK3. Whereas SRPK1 is found predominantly expressed in testicles and pancreas, SRPK2 is mainly found in the brain. Both are found moderately expressed in other human tissues such as skeletal muscle and heart and slightly expressed in the lung, liver, PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19809023 and kidney. The expression of SRPK3 seems to be restricted to muscle cells and it has not been linked to cancer so far. SRPK1 and SRPK2 have been found overexpressed in different types of cancer including breast, colon, pancreatic carcinomas, leukemia, nonsmall cell lung carcinoma, squamous cell lung carcinoma, gliomas, ovary, and hepatocellular carcinoma. Increased SRPK1 expression in breast and colonic cancer has been coordinately correlated to the enhancement of tumor grade. Furthermore, targeting SRPK1 using small interfering RNA in BioMed Research International cell lines of these two tumors resulted in both increased apoptotic potential and enhanced cell killing after treatment with gemcitabine and cisplatin. These findings seemed to be accompanied by reduced phosphorylation of MAPK3, MAPK1, and AKT. In breast cancer cells, increased levels of SRPK1 and the RNA binding protein RBM4 have been related to apoptosis resistance. In leukemia, SRPK2 overexpression has been shown to result in increased cell proliferation due to SR protein A-83-01 manufacturer acinus phosphorylation and cyclin A1 upregulation. These data have been complemented by knockdown experiments whose cyclin A1 expression attenuation and cell arrest at G1 phase were both observed. Overexpression of SRPK1 and SRPK2 has also been found in lung tumors samples in percentages as high as 92% and 94% for lung adenocarcinoma and 72% and 68% for squamous cell lung carcinoma, respectively. Additionally, SRSF2 overexpression has been shown to mostly accumulate under its phosphorylated form in these patient samples in agreement with the observed overexpression of SRPK1 and SRPK2. In patients with ovarian cancer, SRPK1 has been found upregulated in 55% of tumor samples. In vitro experiments conducted with ovarian cell line

Share this post on:

Author: Squalene Epoxidase