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Yy1 Research Paper

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Yin Yang 1 in HCC: YY1 is a transcription factor with complex biological functions, including apoptosis, tumorigenesis, development and differentiationYY1 is a member of the Polycomb Group protein family, a group of homeobox gene receptors that play critical roles in hematopoiesis and cell cycle control [26, 27]. The human YY1 gene is located on the telomere region of human chromosome 14 at the segment q32.2. It consists of five highly conserved exons encoding a protein of 14 amino acids in length, and an estimated molecular weight of 44 kDa. The YY1 protein contains four C2H2-type zinc-finger motifs with two specific domains that characterize its function as an activator or repressor. YY1 is a phosphoprotein with a half-life of 3.5 hours. …show more content…

The function of YY1 in transcription is context-specific and requires interactions with many cellular factors. As a result, YY1 develops intracellular networks that allow it to induce multiple functions in transcriptional initiation, activation and repression, ultimately leading to the regulation of normal cell growth and survival. As a DNA binding protein, YY1 functions in the replication and regulation of the histone alpha complex, vital for proliferating cells[29].Overexpression of YY1 in tumor tissues exerts different clinical behavior in different tumor types. YY1 The loss of YY1 results in a significant increase in p53 levels. YY1, MDM-2 and p53 can form a ternary complex and YY1 is essential for optimal MDM2-p53 physical interactions in vivo, which is a prerequisite for MDM2 to be able to ubiquinate p53. Ubiquitination induces the translocation of p53 to the proteasome which leads to its …show more content…

A large body of literature has documented hyperactivated AKT signaling in human solid tumors and hematological malignancies[34]. The PI3K/AKT/mTOR signaling pathway plays an important role in HCC and is activated in 30%–50% of HCC[35]. Sorafenib does not target this pathway. AKT/mTOR is critical for regulating growth and proliferation in any cell type. Data from HCC clinical trials have revealed that AKT/mTOR pathway is upregulated upon treatment and therefore the cancer acquires resistance to therapy. Cyclin D1 is a downstream target of AKT, which directly regulates cell cycle progression. Of the three highly conserved AKT isoforms, AKT1 is involved in regulating cell proliferation[36]. Accumulating research suggests that PI3K/AKT activation after sorafenib treatment plays a pivotal role in tumor progression in HCC. p-AKT levels increase in HCC cell lines after treating them with sorafenib [11, 37]. Targeting AKT1 will also suppress the activity of its downstream effector pathway

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