E2F-6 contributes to gene silencing in a manner independent of retinoblastoma protein family members. To better elucidate the molecular mechanism repression by E2F-6, we have purified factor from cultured cells. is found multimeric complex that contains Mga and Max, thus can bind not only E2F-binding site but also Myc- Brachyury-binding sites. Moreover, chromatin modifiers such as novel histone methyltransferase modifies lysine 9 H3, HP1γ, Polycomb group (PcG) proteins. The preferentially...

Merkel cell carcinoma (MCC) is a highly aggressive skin cancer that frequently harbours polyomavirus (MCV) DNA integrated in the genome of tumor cells. In our study, we elaborate recent finding MCV-positive MCC lines require expression viral T antigens (TA). Indeed, xeno-transplantation model, prove TA essential also an vivo situation, as knock down leads to regression. Moreover, rescuing short hairpin RNA (shRNA)-treated cells by ectopic shRNA-insensitive TAs clearly demonstrates observed...

The E2F family of transcription factors plays a crucial role in cell cycle progression. activity is tightly regulated by number mechanisms, which include the timely synthesis and degradation E2F, interaction with retinoblastoma protein members (“pocket proteins”), association DP heterodimeric partner proteins, phosphorylation E2F/DP complex. Here we report that another mechanism, subcellular localization, important for regulation activity. Unlike E2F-1, -2, or -3, are constitutively nuclear,...

Here we report the identification of LIN complex (LINC), a human multiprotein that is required for transcriptional activation G2/sub>/M genes. LINC related to recently identified dREAM and DRM complexes Drosophila C.elegans contain homologues mammalian retinoblastoma tumor suppressor protein. The core consists at least five subunits including chromatin-associated LIN-9 RbAp48 proteins. dynamically associates with pocket proteins, E2F B-MYB during cell cycle. In quiescent cells, binds p130...

E2F transcription factors play an important role in the regulation of cell cycle progression. We report here cloning and characterization additional member this family, E2F-6. E2F-6 lacks pocket protein binding transactivation domains, it is a potent transcriptional repressor that contains modular repression domain at its carboxyl terminus. Overproduction had no specific effect on progression asynchronously growing Saos2 NIH 3T3 cells, but inhibited entry into S phase cells stimulated to...

Geoffrey J. Lindeman, Lina Dagnino, Stefan Gaubatz, Yuhui Xu, Roderick T. Bronson, Henry B. Warren, and David M. Livingston The Dana-Farber Cancer Institute/Harvard Medical School, Boston, Massachusetts 02115 USA; Ottawa General Hospital Research Institute, Ottawa, Ontario K1H 8L6 Canada; Tufts University School of Veterinary Medicine, 02111 Center for Animal Resources Comparative Medicine/Harvard USA

In RAT1A fibroblasts, expression of the prothymosin alpha gene is under transcriptional control c-myc proto-oncogene. We have now cloned rat encoding and show that regulated by in vivo. find regulation mediated sequences downstream start site, whereas promoter constitutive not c-myc. identified an enhancer element within first intron sufficient to mediate a response Myc Max transient transfection assays activation estrogen receptor-Myc chimeras this contains consensus Myc-binding site...

Recently, the conserved human LINC/DREAM complex has been described as an important regulator of cell cycle genes. LINC consists a core module that dynamically associates with E2F transcription factors, p130 and B-MYB factor in cycle-dependent manner. In this study, we analyzed evolutionary LIN54 subunit LINC. We found is required for progression. Protein interaction studies demonstrated predicted helix-coil-helix motif B-MYB. addition, cysteine-rich CXC domain novel DNA-binding binds to...

YAP and TAZ, downstream effectors of the Hippo pathway, are important regulators proliferation. Here, we show that ability to activate mitotic gene expression is dependent on Myb-MuvB (MMB) complex, a master regulator genes expressed in G2/M phase cell cycle. By carrying out genome-wide binding analyses, found promotes MMB subunit B-MYB promoters target genes. binds stimulates chromatin association through distal enhancer elements interact with MMB-regulated looping. The cooperation between...

E2F transcription factors play a critical role in the control of cell cycle progression, regulating expression genes involved DNA replication, repair, mitosis, and fate. This involves both positive-acting negative-acting proteins, latter group including E2F6 protein, which has been shown to function as an Rb-independent repressor E2F-target gene transcription. In effort better delineate context function, mechanisms functional specificity, we used chromatin immunoprecipitation assays assess...

The A mating-type factor is one of two gene complexes that allows mating cells the mushroom Coprinus cinereus to recognize self from nonself and regulate a pathway sexual development leads meiosis sporulation. We have identified seven genes separated into subcomplexes corresponding classical alpha beta loci. Four genes, three beta, all coding for proteins with homeo domain-related motif, determine A-factor specificity; their allelic forms are so different in sequence they do not...

c-myc plans a key role in regulating mammalian cell proliferation and apoptosis. The gene codes for transcription factor, Myc, that belongs to the helix-loop-helix/leucine zipper (HLH/LZ) family of proteins. Myc heterodimerizes with partner protein termed Max; heterodimeric complex binds CAC(G/A)TG (E-box) sequences activates from these sites. However, several other HLH/LZ proteins, including USF TFE-3, bind trans-activate same element, yet have no documented effect on or Therefore, it is...

E2F is a family of transcription factors required for normal cell cycle control and arrest in G1. E2F4 the most abundant protein many types. In quiescent cells, it localized to nucleus, where bound retinoblastoma-related p130. During entry into cycle, disappears from nucleus appears cytoplasm. The mechanism by which this change occurs has, past, been unclear. We have found that actively exported leptomycin B, specific inhibitor nuclear export, inhibits process. export mediated two...

In response to DNA damage, several signaling pathways that arrest the cell cycle in G(1) and G(2) are activated. The down-regulation of mitotic genes contributes stable maintenance arrest. human LINC or DREAM complex, together with B-MYB transcription factor, plays an essential role expression G(2)-M genes. Here, we show damage results p53-dependent binding p130 E2F4 dissociation from LINC. We find fails dissociate p53 mutant cells, this increased gene these and, importantly, is required for...

The p16INK4a–RB pathway plays a critical role in preventing inappropriate cell proliferation and is often targeted by viral oncoproteins during immortalization. Latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) present EBV-associated proliferative diseases for the immortalizing transforming activity EBV. Unlike other DNA tumor oncoproteins, which possess activity, LMP1 does not bind to retinoblastoma suppressor protein, but instead blocks expression p16INK4a gene. However, it has...

The retinoblastoma tumor suppressor protein (pRB) and related p107 p130 "pocket proteins" function together with the E2F transcription factors to repress gene expression during cell cycle development.Recent biochemical studies have identified multisubunit DREAM pocket complexes in Drosophila melanogaster Caenorhabditis elegans regulating developmental repression.Although a conserved complex has also been mammalian cells, its physiological vivo not determined.Here we addressed this question...

Melanoma cells are usually characterized by a strong proliferative potential and efficient invasive migration. Among the multiple molecular changes that recorded during progression of this disease, aberrant activation receptor tyrosine kinases (RTK) is often observed. Activation matrix metalloproteases goes along with RTK enhances RTK-driven The purpose study was to examine three-dimensional migration melanocytes pro-tumorigenic role for melanoma cells. Using experimental melanocyte...

The mammalian DREAM complex is key regulator of cell cycle regulated gene transcription and drives the expression many products required for mitosis cytokinesis. In this study we characterized a novel target DREAM, GAS2L3, which belongs to GAS2 family proteins with putative actin microtubule binding domains. We found that GAS2L3 localizes spindle midzone midbody during anaphase cytokinesis, respectively. Biochemical studies show binds bundles microtubules as well F-actin in vitro....