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Proto-Oncogene and Onco-Suppressor Gene Expression
Published in Enrique Pimentel, Handbook of Growth Factors, 2017
The different homo- and heterodimeric Jun/Fos proteins may have similar but distinctive cellular functions.241 A wide diversity of homo- and heterodimeric nuclear proteins may participate in the transcriptional regulation of DNA elements that respond to extracellular signals such as hormones and growth factors. Two major classes of regulatory elements that contribute to this regulation by extracellular signaling agents are the DNA sequence motifs AP-l/TRE and ATF/CRE. The AP-l/TRE element (TGACTCA) is the AP-1 binding site or phorbol ester (TPA) responsive element (TRE). The ATF/CRE element (TGACGTCA) is the activating transcription factor (ATF) binding site or cAMP responsive element (CRE). Several proteins bind to such cw-acting elements.242 The AP-l/TRE site is recognized by a group of proteins that includes those of the Fos and Jun families. The ATF/CRE site is recognized by a family of proteins called ATF or CRE-binding proteins (CREBs). The ATF/CREB family is implicated in cAMP- and calcium-induced alterations in transcription.
The Structural and Functional Roles of Specific Nonhistone Protein Fractions in Chromatin
Published in Isaac Bekhor, Carol J. Mirell, C. C. Liew, Progress in Nonhistone Protein Research, 1985
The maturation of the avian erythrocyte involves a series of nuclear and cytoplasmic events which lead to an almost complete cessation of metabolic function.45–51 During the course of differentiation, the nucleus of the reticulocyte becomes pycnotic with condensed chromatin.45,49,50 DNA and RNA synthesis in these nuclei is severely diminished.45–48 This suggests that the basic transcriptional conformation of the DNA in chromatin has been changed. An examination of the changes in nuclear proteins and chromatin structure might give insight into the nature of the mechanisms involved.
Therapeutic approaches for targeting receptor tyrosine kinase like orphan receptor-1 in cancer cells
Published in Expert Opinion on Therapeutic Targets, 2019
Amin Kamrani, Amir Mehdizadeh, Majid Ahmadi, Leili Aghebati-Maleki, Mehdi Yousefi
A large group of RNAs including tRNA, rRNA, snoRNA, snRNA, siRNA, and miRNA are categorized under the umbrella term of non-coding RNAs group. MiRNAs along with DNA methylation and histone acetylation were introduced as epigenetic mechanisms and play a vital role in regulating gene expression [75]. miRNAs usually have 18 to 23 nucleotides that modulate cell proliferation, growth, and survival [75]. miRNAs include only 1% of the total genome in different species such as humans, however, their expression affects 30% of the total gene function [76]. MiRNAs encoding genes are longer than that of the processed mature miRNA molecule. Many miRNAs genes are located in the host genes intron region of their pre-mRNA and share their regulatory elements, primary transcript, and have similar expression pattern [75] . Few primary miRNA genes transcripts,that are transcribed from their own promoters, are fully discovered and identified [77]. RNA polymerase II transcribes microRNAs as large RNA precursors called pri-miRNAs containing a 5‘ cap and poly-A tail. Microprocessor complex processes the pri-miRNAs in the nucleus which is consisted of the RNase III enzyme Drosha, double-stranded-RNA-binding protein and Pasha/DGCR8. The resulted 70-nucleotides length pre-miRNAs are folded into the imperfect stem-loop structure. Then, the karyopherin exportin 5 (Exp5) and Ran-GTP complex export pre-miRNAs into the cytoplasm [76]. Ran (ras-related nuclear protein), as a small GTP binding protein belonging to the RAS superfamily, is essential for the translocation of RNA and proteins through the nuclear pore complex. A nuclear heterotrimer is formed by the Ran GTPase with pre-miRNAs by binding to Exp5. Then, the pre-miRNAs undergo an additional processing step by the RNAse III enzyme dicer generating the miRNA in the cytoplasm. Dicer also initiates the formation of RNA-Induced Silencing Complex (RISC) responsible for gene silencing due to miRNA expression and RNA interference [76] (Figure 3). miRNAs control gene expression at the post-transcriptional level by binding to 3/-UTR of mRNA inducing the mRNA fragmentation or blockage [78]. MiRNA-mediated suppression of mRNA includes coupling of miRNA with mRNA and the endonucleotide cutting. Here, mRNA is completely fragmented because of the lack of 3/and 5/heading protection and increased susceptibility to exonuclease [79]. However, in animal cells, this event is rarely occurred due to an incomplete match of miRNA and mRNA. In imperfect miRNA-mRNA pairing, poly-A tail will be quickly removed and poly-A associated proteins will be separated following this deadenylation leading to 5/cap separation and exogenous digestion [80]. Many of the known miRNAs are shown to contribute to human cancer metastasis and tumorogenesis by targeting tumor suppressor genes and oncogenes [77,80]