These reports strongly suggest that participates not only in cell proliferation but also in suppressing premature senescence via the recruitment of PRC1 and PRC2 to the locus (Fig.?3a). Open in a separate window Fig.?3 Model showing the proposed mechanisms of locus. cyclin-dependent kinases (CDKs) and their related pathways. CDKs are activated via binding to their selected cyclins in specific phases of the cell cycle, following which they phosphorylate their target proteins. The CDK inhibitors (CKIs) negatively regulate the activities of CDKs and control the cell cycle. pRB regulates G1/S progression. The p53 pathway plays a role in DNA damage response as a gatekeeper of the genome. Several lncRNAs control the expression BI6727 (Volasertib) of cyclins-CDKs, CKIs, pRB and p53, and participate in cell cycle regulation. Some of these lncRNAs are induced by BI6727 (Volasertib) DNA damage and inhibit cell cycle progression by regulating these cell cycle regulators CDKs and their related pathways control the cell cycle by maintaining exit and access to the different phases of the cell cycle. In the G1 phase, growth stimuli such as growth factors often activate the MAP kinase pathway, following which genes encoding the cyclin Ds are transcribed. The producing products bind to and activate CDK4/6 . Cyclin DsCCDK4/6 complexes phosphorylate retinoblastoma protein (pRB) and its family members, p107 and p130, in the late BI6727 (Volasertib) G1 phase and activate E2F-mediated transcription, which induces the BI6727 (Volasertib) expression of several growth-promoting genes [7, 8]. At the G1/S transition point, cyclin E-CDK2 phosphorylates pRB as well as several proteins involved in DNA replication to promote G1/S progression . Cyclin B-CDK1 has many targets including APC/cyclosome, and promotes maturation of the G2 phase and critically participates in M phase events . The cellular levels of cell cycle regulators such as cyclins, CDKs, CDK inhibitors, CDC25, RB, and E2F are critical for cell cycle regulation. After the cell cycle regulators total their functions, they are ubiquitylated by specific E3 ligases and eliminated via the ubiquitinCproteasome pathway [11C13]. The level of cell cycle regulators is usually precisely controlled by not only post-translational but also translational mechanisms. For example, several micro-RNAs (miRNAs) participate in cell cycle regulation through translational regulation . MiRNAs are small non-coding RNA molecules made up of 22 nucleotides, and negatively regulate translation through binding of the untranslated region of its target mRNAs . The let-7 miRNA family negatively regulates cyclins A and D, and CDK4/6 and CDC25A . The miR-15 family also inhibits the translation of cyclin D, CDK4, and CDC27 [17, 18]. Interestingly, these let-7 and miR-15 family members may be involved in tumorigenesis since Rabbit polyclonal to SHP-2.SHP-2 a SH2-containing a ubiquitously expressed tyrosine-specific protein phosphatase.It participates in signaling events downstream of receptors for growth factors, cytokines, hormones, antigens and extracellular matrices in the control of cell growth, they are downregulated in various human cancers [16C18]. Alternatively, cyclin D1 is usually a target for not only let-7 and miR-15 miRNAs but also miR-19a, 26a, and 34a . Furthermore, p27 is usually targeted for regulation by the miR-181 family  and the miR-221 family . The functions of other miRNAs in the expression of cell cycle regulators have also been reported . Thus, it has been shown that this cell cycle regulators are critically and BI6727 (Volasertib) precisely controlled by E3 ligases and miRNAs both post-translationally and at the translational level. Here, we focus on long non-coding RNAs (lncRNAs) involved in the regulation of the cell cycle through their numerous functions as epigenetic regulators, transcription factor regulators, post-transcription regulators and protein scaffolds [21, 22]. LncRNAs are non-protein coding transcripts longer than 200 nucleotides, and can be divided into at least five groups based on their structural characteristics,.