کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5525579 1546673 2017 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mini-reviewSplicing factors of SR and hnRNP families as regulators of apoptosis in cancer
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Mini-reviewSplicing factors of SR and hnRNP families as regulators of apoptosis in cancer
چکیده انگلیسی


- Apoptotic control is dysregulated in cancers.
- Apoptotic genes are alternatively spliced to give pro- and anti-apoptotic proteins.
- Alternative splicing of apoptotic genes is regulated by SR and hnRNP proteins.
- SRs and hnRNPs affect chemoresistance and apoptotic responses in cancer cells.
- SRs and hnRNPs are potential therapeutic targets.

SR and hnRNP proteins were initially discovered as regulators of alternative splicing: the process of controlled removal of introns and selective joining of exons through which multiple transcripts and, subsequently, proteins can be expressed from a single gene. Alternative splicing affects genes involved in all crucial cellular processes, including apoptosis. During cancerogenesis impaired apoptotic control facilitates survival of cells bearing molecular aberrations, contributing to their unrestricted proliferation and chemoresistance. Apparently, SR and hnRNP proteins regulate all levels of expression of apoptotic genes, including transcription initiation and elongation, alternative splicing, mRNA stability, translation, and protein degradation. The frequently disturbed expressions of SR/hnRNP proteins in cancers lead to impaired functioning of target apoptotic genes, including regulators of the extrinsic (Fas, caspase-8, caspase-2, c-FLIP) and the intrinsic pathway (Apaf-1, caspase-9, ICAD), genes encoding Bcl-2 proteins, IAPs, and p53 tumor suppressor. Prototypical members of SR/hnRNP families, SRSF1 and hnRNP A1, promote synthesis of anti-apoptotic splice variants of Bcl-x and Mcl-1, which results in attenuation of programmed cell death in breast cancer and chronic myeloid leukemia. SR/hnRNP proteins significantly affect responses to chemotherapy, acting as mediators or modulators of drug-induced apoptosis. Aberrant expression of SRSF1 and hnRNP K can interfere with tumor responses to chemotherapy in pancreatic and liver cancers. Currently, a number of splicing factor inhibitors is being tested in pre-clinical and clinical trials.In this review we discuss recent findings on the role of SR and hnRNP proteins in apoptotic control in cancer cells as well as their significance in anticancer treatments.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 396, 28 June 2017, Pages 53-65
نویسندگان
, ,