http://www.celldiv.com The latest research articles published by Cell Division 2012-05-15T00:00:00Z This article [Singh et al, Cell Division, 2010, 5:4] is retracted as it contains large amount of text that has been duplicated from other articles previously published. We apologize to all affected parties for the inconvenience caused. http://www.celldiv.com/content/7/1/15 Richa Singh Jasmine George Yogeshwer Shukla Cell Division 2012, null:15 2012-05-15T00:00:00Z doi:10.1186/1747-1028-7-15 /content/figures/1747-1028-7-15-toc.gif Cell Division 1747-1028 ${item.volume} 15 2012-05-15T00:00:00Z PDF Cyclin-dependent kinases (Cdks) and their cyclin regulatory subunits control cell growth and division. Cdk2-cyclin E complexes, phosphorylating the retinoblastoma protein, drive cells through the G1/S transition into the S phase of the cell cycle. Despite its fundamental role, Cdk2 was found to be indispensable only in specific cell types due to molecular redundancies in its function. Converging studies highlight involvement of Cdk2 and associated cell cycle regulatory proteins in oligodendrocyte progenitor cell proliferation and differentiation. Giving the contribution of this immature cell type to brain plasticity and repair in the adult, this review will explore the requirement of Cdk2 for oligodendrogenesis, oligodendrocyte progenitor cells proliferation and differentiation during physiological and pathological conditions. http://www.celldiv.com/content/7/1/14 Celine Caillava Anne Baron-Van Evercooren Cell Division 2012, null:14 2012-05-14T00:00:00Z doi:10.1186/1747-1028-7-14 /content/figures/1747-1028-7-14-toc.gif Cell Division 1747-1028 ${item.volume} 14 2012-05-14T00:00:00Z PDF Background: In Schizosaccharomyces pombe the SET domain protein, Set3p - together with its interacting partners, Snt1p, and Sif2p - form a complex that aids in preventing cell division failure upon mild cytokinetic stress. Intriguingly, the human orthologs of these genes (MLL5, NCOR2, and TBL1X) are also important for the faithful completion of cytokinesis in tissue culture cells. Since MLL5, NCOR2, and TBL1X form a complex with the histone de-acetylase, HDAC3, we sought to determine if an orthologous counterpart played a regulatory role in fission yeast cytokinesis. Results: In this report we identify the hos2 gene as the fission yeast HDAC3 ortholog. We show that Hos2p physically interacts with Set3p, Snt1p, and Sif2p, and that hos2Delta mutants are indeed compromised in their ability to reliably complete cell division in the presence of mild cytokinetic stresses. Furthermore, we demonstrate that over-expression of hos2 causes severe morphological and cytokinetic defects. Lastly, through recombinase mediated cassette exchange, we show that expression of human HDAC3 complements the cytokinetic defects exhibited by hos2Delta cells. Conclusions: These data support a model in which Hos2p functions as a critical functional component of the Set3p-Snt1p-Sif2p complex with respect to its role in cytokinesis. The ability of human HDAC3 to complement the cytokinesis defects associated with the deletion of the hos2 gene suggests that further analysis of this system could translate into a theoretical framework for understanding how the orthologous MLL5 complex functions to regulate cytokinesis in human cells. http://www.celldiv.com/content/7/1/13 Charnpal Grewal Jack Hickmott Stefan Rentas Jim Karagiannis Cell Division 2012, null:13 2012-05-04T00:00:00Z doi:10.1186/1747-1028-7-13 /content/figures/1747-1028-7-13-toc.gif Cell Division 1747-1028 ${item.volume} 13 2012-05-04T00:00:00Z PDF The cyclin-dependent kinases (Cdks) regulate many cellular processes, including the cell cycle, neuronal development, transcription, and posttranscriptional processing. To perform their functions, Cdks bind to specific cyclin subunits to form a functional and active cyclin/Cdk complex. This review is focused on Cyclin K, which was originally considered an alternative subunit of Cdk9, and on its newly identified partners, Cdk12 and Cdk13. We briefly summarize research devoted to each of these proteins. We also discuss the proteins' functions in the regulation of gene expression via the phosphorylation of serine 2 in the C-terminal domain of RNA polymerase II, contributions to the maintenance of genome stability, and roles in the onset of human disease and embryo development. http://www.celldiv.com/content/7/1/12 Jiri Kohoutek Dalibor Blazek Cell Division 2012, null:12 2012-04-18T00:00:00Z doi:10.1186/1747-1028-7-12 /content/figures/1747-1028-7-12-toc.gif Cell Division 1747-1028 ${item.volume} 12 2012-04-18T00:00:00Z XML Background: The Positive Transcription Elongation Factor b (P-TEFb) is a complex of Cyclin Dependent Kinase 9 (CDK9) with either cyclins T1, T2 or K. The complex phosphorylates the C-Terminal Domain of RNA polymerase II (RNAPII) and negative elongation factors, stimulating productive elongation by RNAPII, which is paused after initiation. P-TEFb is recruited downstream of the promoters of many genes, including primary response genes, upon certain stimuli. Flavopiridol (FVP) is a potent pharmacological inhibitor of CDK9 and has been used extensively in cells as a means to inhibit CDK9 activity. Inhibition of P-TEFb complexes has potential therapeutic applications. Results: It has been shown that Lipopolysaccharide (LPS) stimulates the recruitment of P-TEFb to Primary Response Genes (PRGs) and proposed that P-TEFb activity is required for their expression, as the CDK9 inhibitor DRB prevents localization of RNAPII in the body of these genes. We have previously determined the effects of FVP in global gene expression in a variety of cells and surprisingly observed that FVP results in potent upregulation of a number of PRGs in treatments lasting 4-24 h. Because inhibition of CDK9 activity is being evaluated in pre-clinical and clinical studies for the treatment of several pathologies, it is important to fully understand the short and long term effects of its inhibition. To this end, we determined the immediate and long-term effect of FVP in the expression of several PRGs. In exponentially growing normal human fibroblasts, the expression of several PRGs including FOS, JUNB, EGR1 and GADD45B, was rapidly and potently downregulated before they were upregulated following FVP treatment. In serum starved cells re-stimulated with serum, FVP also inhibited the expression of these genes, but subsequently, JUNB, GADD45B and EGR1 were upregulated in the presence of FVP. Chromatin Immunoprecipitation of RNAPII revealed that EGR1 and GADD45B are transcribed at the FVP-treatment time points where their corresponding mRNAs accumulate. These results suggest a possible stress response triggered by CDK9 inhibition than ensues transcription of certain PRGs. Conclusions: We have shown that certain PRGs are transcribed in the presence of FVP in a manner that might be independent of CDK9, suggesting a possible alternative mechanism for their transcription when P-TEFb kinase activity is pharmacologically inhibited. These results also show that the sensitivity to FVP is quite variable, even among PRGs. http://www.celldiv.com/content/7/1/11 Havva Keskin Judit Garriga Daphne Georlette Xavier Grana Cell Division 2012, null:11 2012-03-29T00:00:00Z doi:10.1186/1747-1028-7-11 /content/figures/1747-1028-7-11-toc.gif Cell Division 1747-1028 ${item.volume} 11 2012-03-29T00:00:00Z XML The retinoblastoma (RB) family of proteins are found in organisms as distantly related as humans, plants, and insects. These proteins play a key role in regulating advancement of the cell division cycle from the G1 to S-phases. This is achieved through negative regulation of two important positive regulators of cell cycle entry, E2F transcription factors and cyclin dependent kinases. In growth arrested cells transcriptional activity by E2Fs is repressed by RB proteins. Stimulation of cell cycle entry by growth factor signaling leads to activation of cyclin dependent kinases. They in turn phosphorylate and inactivate the RB family proteins, leading to E2F activation and additional cyclin dependent kinase activity. This propels the cell cycle irreversibly forward leading to DNA synthesis. This review will focus on the basic biochemistry and cell biology governing the regulation and activity of mammalian RB family proteins in cell cycle control. http://www.celldiv.com/content/7/1/10 Shauna Henley Frederick Dick Cell Division 2012, null:10 2012-03-14T00:00:00Z doi:10.1186/1747-1028-7-10 /content/figures/1747-1028-7-10-toc.gif Cell Division 1747-1028 ${item.volume} 10 2012-03-14T00:00:00Z XML Background: Ubiquitin-dependent protein degradation is a critical step in key cell cycle events, such as metaphase-anaphase transition and mitotic exit. The anaphase promoting complex/cyclosome (APC/C) plays a pivotal role in these transitions by recognizing and marking regulatory proteins for proteasomal degradation. Its overall structure and function has been elucidated mostly in yeasts and mammalian cell lines. The APC/C is, however, a multisubunit assembly with at least 13 subunits and their function and interaction within the complex is still relatively uncharacterized, particularly in metazoan systems. Here, lemming (lmg) mutants were used to study the APC/C subunit, Apc11, and its interaction partners in Drosophila melanogaster. Results: The lmg gene was initially identified through a pharate adult lethal P element insertion mutation expressing developmental abnormalities and widespread apoptosis in larval imaginal discs and pupal abdominal histoblasts. Larval neuroblasts were observed to arrest mitosis in a metaphase-like state with highly condensed, scattered chromosomes and frequent polyploidy. These neuroblasts contain high levels of both cyclin A and cyclin B. The lmg gene was cloned by virtue of the lmg03424 P element insertion which is located in the 5' untranslated region. The lemming locus is transcribed to give a 2.0 kb mRNA that contains two ORFs, lmgA and lmgB. The lmgA ORF codes for a putative protein with more than 80% sequence homology to the APC11 subunit of the human APC/C. The 85 amino acid protein also contains a RING-finger motif characteristic of known APC11 subunits. The lmgA ORF alone was sufficient to rescue the lethal and mitotic phenotypes of the lmg138 null allele and to complement the temperature sensitive lethal phenotype of the APC11-myc9 budding yeast mutant. The LmgA protein interacts with Mr/Apc2, and they together form a binding site for Vihar, the E2-C type ubiquitin conjugating enzyme. Despite being conserved among Drosophila species, the LmgB protein is not required for viability or fertility. Conclusions: Our work provides insight into the subunit structure of the Drosophila APC/C with implications for its function. Based on the presented data, we suggest that the Lmg/Apc11 subunit recruits the E2-C type ubiquitin conjugating enzyme, Vihar, to the APC/C together with Mr/Apc2 by forming a ternary complex. http://www.celldiv.com/content/7/1/9 Olga Nagy Margit Pal Andor Udvardy Christine Shirras Imre Boros Alan Shirras Peter Deak Cell Division 2012, null:9 2012-03-14T00:00:00Z doi:10.1186/1747-1028-7-9 /content/figures/1747-1028-7-9-toc.gif Cell Division 1747-1028 ${item.volume} 9 2012-03-14T00:00:00Z PDF Background: Xylopia aethiopica, a plant found throughout West Africa, has both nutritional and medicinal uses. The present study aims to characterize the effects of extracts of this plant on cancer cells. Results: We report that X. aethiopica extract prepared with 70% ethanol has antiproliferative activity against a panel of cancer cell lines. The IC50 was estimated at 12 μg/ml against HCT116 colon cancer cells, 7.5 μg/ml and > 25 μg/ml against U937 and KG1a leukemia cells, respectively. Upon fractionation of the extract by HPLC, the active fraction induced DNA damage, cell cycle arrest in G1 phase and apoptotic cell death. By using NMR and mass spectrometry, we determined the structure of the active natural product in the HPLC fraction as ent-15-oxokaur-16-en-19-oic acid. Conclusion: The main cytotoxic and DNA-damaging compound in ethanolic extracts of Xylopia aethiopica is ent-15-oxokaur-16-en-19-oic acid. http://www.celldiv.com/content/7/1/8 Aphrodite Choumessi Mathieu Danel Stefan Chassaing Isabelle Truchet Veronique Penlap Anatole Pieme Tazoacha Asonganyi Bernard Ducommun Annie Valette Cell Division 2012, null:8 2012-03-12T00:00:00Z doi:10.1186/1747-1028-7-8 /content/figures/1747-1028-7-8-toc.gif Cell Division 1747-1028 ${item.volume} 8 2012-03-12T00:00:00Z XML Abstact Background: The inorganic phosphate (Pi) transporter, PiT1 (SLC20A1), is ubiquitously expressed in mammalian cells. It has previously been shown that down-regulation of PiT1 severely impaired the proliferation of two transformed human cells lines, HepG2 and HeLa, and the tumorigenicity of HeLa cells in nude mice. Moreover, PiT1 knock-out mice do not survive past E12.5 and from E10.5, the embryos were found to be growth-retarded and showed reduced proliferation of liver cells. Isolated mouse embryonic fibroblasts with knocked out as well as reduced PiT1 expression levels also exhibited impaired proliferation. Together these results suggest that a certain level of PiT1 is important for proliferation. We have here investigated the role of PiT1 in regulation of cell proliferation using two strictly density-inhibited cells lines, the murine MC3T3-E1 and NIH3T3 cells. Results: We found that knock-down of PiT1 in MC3T3-E1 cells led to impaired proliferation supporting that at least a certain level of PiT1 is important for wildtype level of proliferation. We, however, also observed that MC3T3-E1 and NIH3T3 cells themselves regulate their endogenous PiT1 mRNA levels with lower levels in general correlating with decreased proliferation/increased cell density. Moreover, over-expression of human PiT1 led to increased proliferation of both MC3T3-E1 and NIH3T3 cultures and resulted in higher cell densities in cultures of these two strictly density-inhibited cell lines. In addition, when we transformed NIH3T3 cells by cultivation in fetal bovine serum, cells over-expressing human PiT1 formed more colonies in soft agar than control cells. Conclusions: We conclude that not only is a certain level of PiT1 necessary for normal cell division as suggested by previously published studies, rather the cellular PiT1 level is involved in regulating cell proliferation and cell density and an increased PiT1 expression can indeed make NIH3T3 cells more sensitive to transformation. We have thus provided the first evidence for that expression of the type III Pi transporter, PiT1, above the endogenous level can drive cell proliferation and overrule cell density constraints, and the results bridge previous observations showing that a certain PiT1 level is important for regulating normal embryonic growth/development and for tumorigenicity of HeLa cells. http://www.celldiv.com/content/7/1/7 Kristina Byskov Nina Jensen Iben Kongsfelt Maria Wielsoe Lasse Pedersen Christa Haldrup Lene Pedersen Cell Division 2012, null:7 2012-03-06T00:00:00Z doi:10.1186/1747-1028-7-7 /content/figures/1747-1028-7-7-toc.gif Cell Division 1747-1028 ${item.volume} 7 2012-03-06T00:00:00Z XML Activation of oncogenes is generally associated with the induction of DNA damage response (DDR) signaling, which acts as a barrier to tumor progression. In this review we will present an overview of the DDR associated with oncogenic activation of Myc, with special focus on two opposite and paradoxical aspects of this response: (1) the role of the Myc-induced DDR in tumor suppression; (2) its role in dampening Myc-induced replication stress, thereby protecting the viability of prospective cancer cells. These opposing effects on cancer progression are controlled by two different branches of DDR signaling, respectively ATM/CHK2 and ATR/CHK1. Indeed, while ATM activity constitutes a barrier to malignant transformation, full activation of ATR and CHK1 is essential for tumor maintenance, providing important opportunities for therapeutic intervention. Thus, the Myc-induced DDR acts as a double-edged sword in tumor progression. http://www.celldiv.com/content/7/1/6 Stefano Campaner Bruno Amati Cell Division 2012, null:6 2012-02-28T00:00:00Z doi:10.1186/1747-1028-7-6 /content/figures/1747-1028-7-6-toc.gif Cell Division 1747-1028 ${item.volume} 6 2012-02-28T00:00:00Z XML