42 research outputs found
Regulation of the MAD1 promoter by G-CSF
MAD family proteins are transcriptional repressors that antagonize the functions of MYC oncoproteins. In particular, MAD1 has been demonstrated to interfere with MYC-induced proliferation, transformation and apoptosis. The MAD1 gene is expressed in distinct patterns, mainly associated with differentiation and quiescence. We observed that MAD1 is directly activated by G-CSF in promyelocytic cell lines. To investigate the transcriptional regulation of the human MAD1 gene, we have cloned and characterized its promoter. A region of high homology between the MAD1 orthologs of human, mouse and rat contains the core promoter, marked by open chromatin, high GC content and the lack of a TATA box. Using deletion constructs we identified two CCAAT-boxes occupied by C/EBPΞ± and Ξ² in the homology region that mediate responsiveness to G-CSF receptor signaling. The necessary signals include the activation of STAT3 and the RAS/RAF/ERK pathway. STAT3 does not bind directly to promoter DNA, but is recruited by C/EBPΞ². In summary, our studies provide a first analysis of the MAD1 promoter and suggest STAT3 functions as a C/EBPΞ² cofactor in the regulation of the MAD1 gene. Our findings provide the base for the characterization of additional signal transduction pathways that control the expression of MAD1
ΠΠΏΡΠΈΠΌΠΈΠ·Π°ΡΠΈΡ ΡΡΠ»ΠΎΠ²ΠΈΠΉ Π΄Π»Ρ ΠΊΠΎΠ½ΡΡΠΎΠ»Ρ ΠΊΠ°ΡΠ΅ΡΡΠ²Π° Π½Π°ΠΏΠΎΠ»Π½ΠΈΡΠ΅Π»Ρ Π² ΠΌΠ΅ΡΠ°Π»Π»ΠΈΡΠ΅ΡΠΊΠΈΡ ΡΡΡΠ±ΠΊΠ°Ρ
ΠΡΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π° Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΡΠΈΡΡΠΎΠ²ΠΎΠΉ ΡΠ°Π΄ΠΈΠΎΠ³ΡΠ°ΡΠΈΠΈ ΠΊΠΎΠ½ΡΡΠΎΠ»ΠΈΡΠΎΠ²Π°ΡΡ ΠΊΠ°ΡΠ΅ΡΡΠ²ΠΎ Π½Π°ΠΏΠΎΠ»Π½ΠΈΡΠ΅Π»Ρ Π² Π΄Π΅ΡΠΎΠ½ΠΈΡΡΡΡΠ΅ΠΌ ΡΠ½ΡΡΠ΅ Ρ ΡΠ΅Π»ΡΡ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ΠΈΡ ΡΠ°Π·Π½ΠΎΠΏΠ»ΠΎΡΠ½ΡΡ
Π²ΠΊΠ»ΡΡΠ΅Π½ΠΈΠΉ, ΡΠ°Π·ΡΡΠ²ΠΎΠ² ΠΈ Π΄ΡΡΠ³ΠΈΡ
ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
Π½Π°ΡΡΡΠ΅Π½ΠΈΠΉ. ΠΡΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Ρ Π·Π°ΠΊΠΎΠ½ΠΎΠΌΠ΅ΡΠ½ΠΎΡΡΠΈ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΉ ΠΈΠ½ΡΠ΅Π½ΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΏΡΠΎΡΠ΅Π΄ΡΠ΅Π³ΠΎ ΠΏΠΎΡΠΎΠΊΠ° ΠΊΠ²Π°Π½ΡΠΎΠ² Π² Π³Π΅ΠΎΠΌΠ΅ΡΡΠΈΠΈ ΡΠ·ΠΊΠΎΠ³ΠΎ ΠΏΡΡΠΊΠ°. ΠΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Π° ΡΠ½Π΅ΡΠ³ΠΈΡ ΡΠ΅Π½ΡΠ³Π΅Π½ΠΎΠ²ΡΠΊΠΎΠ³ΠΎ ΠΈΠ·Π»ΡΡΠ΅Π½ΠΈΡ, ΠΎΠ±Π΅ΡΠΏΠ΅ΡΠΈΠ²Π°ΡΡΠ°Ρ ΠΌΠ°ΠΊΡΠΈΠΌΠ°Π»ΡΠ½ΡΠΉ ΠΏΠ΅ΡΠ΅ΠΏΠ°Π΄ ΠΈΠ½ΡΠ΅Π½ΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΏΡΠΎΡΠ΅Π΄ΡΠ΅Π³ΠΎ ΠΏΠΎΡΠΎΠΊΠ° ΠΏΡΠΈ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΈ ΠΏΠ»ΠΎΡΠ½ΠΎΡΡΠΈ Π½Π°ΠΏΠΎΠ»Π½ΠΈΡΠ΅Π»Ρ Π½Π° +-30 %
The influence of annealings on structure and microhardness of Fe-Mo-V-Nb-C steel processed by high-pressure torsion
The influence of high-pressure torsion on microstructure, microhardness and thermal stability of lowcarbon steel Fe-0,1Mo-0,6Mn-0,8Cr-0,2Ni-0,3Si-0,2Cu-0,1V-0,06Nb-0,09C, (wt.%) was investigated. It was shown that ultrafine-grained structure formed by high-pressure torsion possesses a high microhardness (H[mu]=7,0 GPa) and high thermal stability up to the temperature of 400Β°Π‘
The regulation of SIRT2 function by cyclin-dependent kinases affects cell motility
Cyclin-dependent kinases (Cdks) fulfill key functions in many cellular processes, including cell cycle progression and cytoskeletal dynamics. A limited number of Cdk substrates have been identified with few demonstrated to be regulated by Cdk-dependent phosphorylation. We identify on protein expression arrays novel cyclin EβCdk2 substrates, including SIRT2, a member of the Sirtuin family of NAD+-dependent deacetylases that targets Ξ±-tubulin. We define Ser-331 as the site phosphorylated by cyclin EβCdk2, cyclin AβCdk2, and p35βCdk5 both in vitro and in cells. Importantly, phosphorylation at Ser-331 inhibits the catalytic activity of SIRT2. Gain- and loss-of-function studies demonstrate that SIRT2 interfered with cell adhesion and cell migration. In postmitotic hippocampal neurons, neurite outgrowth and growth cone collapse are inhibited by SIRT2. The effects provoked by SIRT2, but not those of a nonphosphorylatable mutant, are antagonized by Cdk-dependent phosphorylation. Collectively, our findings identify a posttranslational mechanism that controls SIRT2 function, and they provide evidence for a novel regulatory circuitry involving Cdks, SIRT2, and microtubules
Model of material and financial flows in the forest industry cluster of the Tomsk region
The main objective of the paper is the modeling of the timber industry complex in the Tomsk region from circular economy and sustainable development point of view. On the basis of the value chain process and the formation of threats along the whole chain nature (forest) - economy - society (consumer) the modeling of products and waste creation has been developed. The large amount of unused waste requires the development of a special regional forestry cluster model using circular economy approach in order to propose best solutions for recycling
Tight correlation between expression of the Forkhead transcription factor FOXM1 and HER2 in human breast cancer
BACKGROUND: FOXM1 regulates expression of cell cycle related genes that are essential for progression into DNA replication and mitosis. Consistent with its role in proliferation, elevated expression of FOXM1 has been reported in a variety of human tumour entities. FOXM1 is a gene of interest because recently chemical inhibitors of FOXM1 were described to limit proliferation and induce apoptosis in cancer cells in vitro, indicating that FOXM1 inhibitors could represent useful anticancer therapeutics. METHODS: Using immunohistochemistry (IHC) we systematically analysed FOXM1 expression in human invasive breast carcinomas (n = 204) and normal breast tissues (n = 46) on a tissue microarray. Additionally, using semiquantitative realtime PCR, a collection of paraffin embedded normal (n = 12) and cancerous (n = 25) breast tissue specimens as well as benign (n = 3) and malignant mammary cell lines (n = 8) were investigated for FOXM1 expression. SPSS version 14.0 was used for statistical analysis. RESULTS: FOXM1 was found to be overexpressed in breast cancer in comparison to normal breast tissue both on the RNA and protein level (e.g. 8.7 fold as measured by realtime PCR). We found a significant correlation between FOXM1 expression and the HER2 status determined by HER2 immunohistochemistry (P < 0.05). Univariate survival analysis showed a tendency between FOXM1 protein expression and unfavourable prognosis (P = 0.110). CONCLUSION: FOXM1 may represent a novel breast tumour marker with prognostic significance that could be included into multi-marker panels for breast cancer. Interestingly, we found a positive correlation between FOXM1 expression and HER2 status, pointing to a potential role of FOXM1 as a new drug target in HER2 resistant breast tumour, as FOXM1 inhibitors for cancer treatment were described recently. Further studies are underway to analyse the potential interaction between FOXM1 and HER2, especially whether FOXM1 directly activates the HER2 promoter
Modes of Interaction of KMT2 Histone H3 Lysine 4 Methyltransferase/COMPASS Complexes with Chromatin
Regulation of gene expression is achieved by sequence-specific transcriptional regulators, which convey the information that is contained in the sequence of DNA into RNA polymerase activity. This is achieved by the recruitment of transcriptional co-factors. One of the consequences of co-factor recruitment is the control of specific properties of nucleosomes, the basic units of chromatin, and their protein components, the core histones. The main principles are to regulate the position and the characteristics of nucleosomes. The latter includes modulating the composition of core histones and their variants that are integrated into nucleosomes, and the post-translational modification of these histones referred to as histone marks. One of these marks is the methylation of lysine 4 of the core histone H3 (H3K4). While mono-methylation of H3K4 (H3K4me1) is located preferentially at active enhancers, tri-methylation (H3K4me3) is a mark found at open and potentially active promoters. Thus, H3K4 methylation is typically associated with gene transcription. The class 2 lysine methyltransferases (KMTs) are the main enzymes that methylate H3K4. KMT2 enzymes function in complexes that contain a necessary core complex composed of WDR5, RBBP5, ASH2L, and DPY30, the so-called WRAD complex. Here we discuss recent findings that try to elucidate the important question of how KMT2 complexes are recruited to specific sites on chromatin. This is embedded into short overviews of the biological functions of KMT2 complexes and the consequences of H3K4 methylation