Aneuploidy and chromosomal instability in cancer: a jackpot to chaos
Genomic instability (GIN) is a hallmark of cancer cells that facilitates the acquisition of mutations conferring aggressive or drug-resistant phenotypes during cancer evolution. Chromosomal instability (CIN) i... (Source: Cell Division)
Source: Cell Division - May 20, 2015 Category: Cytology Authors: Maybelline Giam and Giulia Rancati Source Type: research
Aneuploidy and chromosomal instability in cancer: a jackpot to chaos
Genomic instability (GIN) is a hallmark of cancer cells that facilitates the acquisition of mutations conferring aggressive or drug-resistant phenotypes during cancer evolution. Chromosomal instability (CIN) is a form of GIN that involves frequent cytogenetic changes leading to changes in chromosome copy number (aneuploidy). While both CIN and aneuploidy are common characteristics of cancer cells, their roles in tumor initiation and progression are unclear. On the one hand, CIN and aneuploidy are known to provide genetic variation to allow cells to adapt in changing environments such as nutrient fluctuations and hypoxia. P...
Source: Cell Division - May 20, 2015 Category: Cytology Authors: Maybelline GiamGiulia Rancati Source Type: research
Mutations in the PCNA-binding site of CDKN1C inhibit cell proliferation by impairing the entry into S phase
CDKN1C (also known as P57 kip2 ) is a cyclin-dependent kinase inhibitor that functions as a negative regulator of cell proliferation through G1 ... (Source: Cell Division)
Source: Cell Division - March 28, 2015 Category: Cytology Authors: Kleiton S Borges, Valerie A Arboleda and Eric Vilain Source Type: research
Mutations in the PCNA-binding site of CDKN1C inhibit cell proliferation by impairing the entry into S phase
CDKN1C (also known as P57
kip2
) is a cyclin-dependent kinase inhibitor that functions as a negative regulator of cell proliferation through G1 phase cell cycle arrest. Recently, our group described gain-of-function mutations in the PCNA-binding site of CDKN1C that result in an undergrowth syndrome called IMAGe Syndrome (Intrauterine Growth Restriction, Metaphyseal dysplasia, Adrenal hypoplasia, and Genital anomalies), with life-threatening consequences. Loss-of-function mutations in CDKN1C have been identified in 5-10% of individuals with Beckwith-Wied...
Source: Cell Division - March 28, 2015 Category: Cytology Authors: Kleiton BorgesValerie ArboledaEric Vilain Source Type: research
Cyclin E2 is the predominant E-cyclin associated with NPAT in breast cancer cells
Conclusions:
The preferential localisation of cyclin E1 or cyclin E2 to distinct foci indicates that each E-cyclin has unique roles. Cyclin E2 uniquely interacts with NPAT in breast cancer cells, and is associated with higher levels of histones in breast cancer. This could explain the unique correlations of high cyclin E2 expression with poor outcome and genomic instability in breast cancer. (Source: Cell Division)
Source: Cell Division - February 19, 2015 Category: Cytology Authors: Samuel RogersBrian GlossChristine LeeClaudio SergioMarcel DingerElizabeth MusgroveAndrew BurgessCatherine Caldon Source Type: research
Differential distribution of HP1 proteins after trichostatin a treatment influences chromosomal stability in HCT116 and WI-38 cells
Background:
Heterochromatin protein 1 (HP1) is important in the establishment, propagation, and maintenance of constitutive heterochromatin, especially at the pericentromeric region. HP1 might participate in recruiting and directing Mis12 to the centromere during interphase, and HP1 disruption or abrogation might lead to the loss of Mis12 incorporation into the kinetochore. Therefore, the centromere structure and kinetochore relaxation that are promoted in the absence of Mis12 could further induce chromosome instability (CIN) by reducing the capacity of the kinetochore to anchor microtubules. The aim of this study was to d...
Source: Cell Division - December 30, 2014 Category: Cytology Authors: Rodrigo González-BarriosErnesto Soto-ReyesRicardo Quiroz-BaezEunice Fabián-MoralesJosé Díaz-ChávezVictor del CastilloJulia MendozaAlejandro López-SaavedraClementina CastroLuis Herrera Source Type: research
Polar electrostatic forces drive poleward chromosome motions
Recent experiments revealing nanoscale electrostatic force generation at kinetochores for chromosome motions have prompted models for interactions between positively charged molecules in kinetochores and negative charge at and near the plus ends of microtubules. A clear picture of how kinetochores and centrosomes establish and maintain a dynamic coupling to microtubules for force generation during the complex motions of mitosis remains elusive. The molecular cell biology paradigm requires that specific molecules, or molecular geometries, for polar force generation be identified. While progress has been made regarding expla...
Source: Cell Division - December 30, 2014 Category: Cytology Authors: Lucian GagliardiDaniel Shain Source Type: research
Differential distribution of HP1 proteins after trichostatin a treatment influences chromosomal stability in HCT116 and WI-38 cells
Background:
Heterochromatin protein 1 (HP1) is important in the establishment, propagation, and maintenance of constitutive heterochromatin, especially at the pericentromeric region. HP1 might participate in recruiting and directing Mis12 to the centromere during interphase, and HP1 disruption or abrogation might lead to the loss of Mis12 incorporation into the kinetochore. Therefore, the centromere structure and kinetochore relaxation that are promoted in the absence of Mis12 could further induce chromosome instability (CIN) by reducing the capacity of the kinetochore to anchor microtubules. The aim of this study was to d...
Source: Cell Division - December 30, 2014 Category: Cytology Authors: Rodrigo González-BarriosErnesto Soto-ReyesRicardo Quiroz-BaezEunice Fabián-MoralesJosé Díaz-ChávezVictor del CastilloJulia MendozaAlejandro López-SaavedraClementina CastroLuis Herrera Source Type: research
Differential expression of centrosome regulators in Her2+ breast cancer cells versus non-tumorigenic MCF10A cells
Centrosome amplification (CA) amongst particular breast cancer subtypes (Her2+ subtype) is associated with genomic instability and aggressive tumor phenotypes. However, changes in signaling pathways associated with centrosome biology have not been fully explored in subtype specific models. Novel centrosome regulatory genes that are selectively altered in Her2+ breast cancer cells are of interest in discerning why CA is more prevalent in this subtype. To determine centrosome/cell cycle genes that are altered in Her2+ cells that display CA (HCC1954) versus non-tumorigenic cells (MCF10A), we carried out a gene microarray. Exp...
Source: Cell Division - September 25, 2014 Category: Cytology Authors: Mi-Young LeeMihaela MarinaJamie KingHarold Saavedra Source Type: research
Smurf2 E3 ubiquitin ligase modulates proliferation and invasiveness of breast cancer cells in a CNKSR2 dependent manner
Conclusions:
Our results therefore suggest a novel relation between Smurf2 and CNKSR2 thereby regulating AKT-dependent cell proliferation and invasion. Owing to the fact that PI3K-AKT signaling is hyperactivated in various human cancers and that Smurf2 also regulates cellular transformation, our results indicate that Smurf2 may serve as a potential molecule for targeted cancer therapy of certain tumour types including breast cancer. (Source: Cell Division)
Source: Cell Division - August 31, 2014 Category: Cytology Authors: Diana DavidSankar JagadeeshanRamkumar HariharanAsha NairRadhakrishna Pillai Source Type: research
The DNA repair component Metnase regulates Chk1 stability
Chk1 both arrests replication forks and enhances repair of DNA damage by phosphorylation of downstream effectors. Metnase (also termed SETMAR) is a SET histone methylase and transposase nuclease protein that promotes both DNA double strand break (DSB) repair and re-start of stalled replication forks. We previously found that Chk1 phosphorylation of Metnase on S495 enhanced its DNA DSB repair activity but decreased its ability to re-start stalled replication forks. Here we show that phosphorylated Metnase feeds back to increase the half-life of Chk1. Chk1 half-life is regulated by DDB1 targeting it to Cul4A for ubiquitinati...
Source: Cell Division - July 9, 2014 Category: Cytology Authors: Elizabeth WilliamsonYuehan WuSudha SinghMichael ByrneJustin WraySuk-Hee LeeJac NickoloffRobert Hromas Source Type: research
The COP9 signalosome subunit 6 (CSN6): a potential oncogene
CSN6 is one subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN), which is an evolutionarily conserved multiprotein complex found in plants and animals and originally described as a repressor of light-dependent growth and transcription in Arabidopsis. CSN is homologous to the 19S lid subcomplex of the 26S proteasome, thus it has been postulated to be a regulator of the ubiquitin-proteasome pathway. In mammalian cells, it consists of eight subunits (CSN1-CSN8). Among the CSN subunits, CSN5 and CSN6 are the only two that each contains an MPN (Mpr1p and Pad1p N-terminal) domain. The deneddylating activity...
Source: Cell Division - November 28, 2013 Category: Cytology Authors: Shang-Nuan ZhangDong-Sheng PeiJun-Nian Zheng Source Type: research
Defining a new vision for the Retinoblastoma gene: report from the 3rd International Rb Meeting
The retinoblastoma tumor suppressor (Rb) pathway is mutated in most, if not all human tumors. In the G0/G1 phase, Rb and its family members p107 and p130 inhibit the E2F family of transcription factors. In response to mitogenic signals, Cyclin-dependent kinases (CDKs) phosphorylate Rb family members, which results in the disruption of complexes between Rb and E2F family members and in the transcription of genes essential for S phase progression. Beyond this role in early cell cycle decisions, Rb family members regulate DNA replication and mitosis, chromatin structure, metabolism, cellular differentiation, and cell death. W...
Source: Cell Division - November 21, 2013 Category: Cytology Authors: Seth RubinJulien Sage Source Type: research
Cohesin loading factor Nipbl localizes to chromosome axes during mammalian meiotic prophase
Conclusions:
Our data propose that cohesin loading activity is maintained during early stages of meiotic prophase in mammalian spermatocytes and oocytes. (Source: Cell Division)
Source: Cell Division - August 22, 2013 Category: Cytology Authors: Katarzyna KuleszewiczXiangwei FuNobuaki Kudo Source Type: research
