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Nuclear Functions (nuclear + function)
Selected AbstractsBCL11A is a SUMOylated protein and recruits SUMO-conjugation enzymes in its nuclear bodyGENES TO CELLS, Issue 9 2008Takeshi Kuwata BCL11A/EVI9 is a zinc-finger protein predominantly expressed in brain and hematopoietic cells. Previous studies show that BCL11A is involved in acute myelomonocytic leukemia and chronic lymphoid leukemia in mouse and human, respectively. Moreover, BCL11A is localized in the characteristic nuclear body in which BCL6 is co-localized. However, the significance of BCL11A in leukemogenesis and nuclear function remains unknown. In this study we show that BCL11A interacts with UBC9, a small ubiquitin-like modifier (SUMO) E2 conjugating enzyme, and recruits SUMO1 into the nuclear body. A lysine residue at amino acid 634 of BCL11A is SUMOylated but not required for the SUMO1 recruitment. The N-terminal region of BCL11A is responsible for SUMO1 recruitment as well as its nuclear body formation. We also show that SENP2, a SUMO specific peptidase, is co-localized in the nuclear body. These results suggest that BCL11A could be involved in the SUMO conjugation system, and that BCL11A might play an important role in protein modification. [source] Subcellular alteration of glyceraldehyde-3-phosphate dehydrogenase in Alzheimer's disease fibroblastsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2003Jennifer L. Mazzola Abstract The regulation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been implicated both in age-related neurodegenerative disease and in apoptosis. Previous in vitro studies suggest an interaction between GAPDH and the ,-amyloid precursor protein (,-APP), a protein directly involved in Alzheimer's disease (AD). New studies indicate that GAPDH is a multidimensional protein with diverse membrane, cytoplasmic, and nuclear functions; each is distinct from its role in glycolysis. The nuclear functions of GAPDH include a role in apoptosis that requires its translocation to the nucleus. Accordingly, ,-APP,GAPDH interactions, altering GAPDH structure in vivo, may affect energy generation, inducing hypometabolism, a characteristic AD phenotype. Because GAPDH is a multifunctional protein, pleiotropic effects may also occur in a variety of fundamental cellular pathways in AD cells. This may include unique GAPDH,RNA interactions. We report here the identification of a high-molecular-weight (HMW) GAPDH species present exclusively in the postnuclear fraction of AD cells. The latter is characterized by reduced GAPDH activity. The HMW GAPDH species was not detected in postnuclear age-matched control (AMC) fractions nor in AD whole-cell preparations. Each is characterized by normal GAPDH activity. By definition, the preparation of whole-cell extracts entails the destruction of subcellular structure. The latter findings indicate that the dissociation of the GAPDH protein from the HMW species restores its enzymatic activity. Thus, these results reveal a new, unique intracellular phenotype in AD cells. The functional consequences of subcellular alteration in GAPDH structure in AD cells are considered. © 2002 Wiley-Liss, Inc. [source] Ultrastructural and immunocytochemical analyses of opioid treatment effects on PC3 prostatic cancer cellsMICROSCOPY RESEARCH AND TECHNIQUE, Issue 3 2004Beatrice Baldelli Abstract Some opioid peptides are able to inhibit the growth of human prostatic cancer cells; in particular, the [D-Ala2,D-Leu5] enkephalin (DADLE) reduces PC3 cell growth. In order to understand how DADLE decreases cell proliferation, we investigated, by electron microscopy, its effects on PC3 cellular components. PC3 cells were incubated with DADLE and processed for both ultrastructural morphology and immunoelectron microscopy. Some cells were incubated with BrU to determine the transcriptional rate. BrU and DADLE molecules were detected by immunogold techniques and the labeling was quantitatively evaluated. Modifications of some cytoplasmic and nuclear components were observed in DADLE-treated cells. Moreover, treated cells incorporated lower amounts of BrU than control cells. DADLE molecules were located in the cytoplasm and in the nucleus, especially on mRNA transcription and early splicing sites. Our data suggest that DADLE is able to slow down the synthetic activity of PC3 cells, perhaps interfering with nuclear functions. Microsc. Res. Tech. 64:243,249, 2004. © 2004 Wiley-Liss, Inc. [source] Immunolocalization of the High-Mobility Group N2 protein and acetylated histone H3K14 in early developing parthenogenetic bovine embryos derived from oocytes of high and low developmental competenceMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 2 2008Guilherme M. Bastos Abstract This study investigated differences in the distribution of acetylated histone H3 at Lysine 14 (H3K14ac) and the High-Mobility Group N2 (HMGN2) protein in the chromatin of early- (before 24 hr) and late-cleaved (after 24 hr) bovine embryos derived from small- (1,2 mm) and large-follicles (4,8 mm). The presence of HMGN2 and H3K14ac has been associated with different nuclear functions including chromatin condensation, transcription, DNA replication and repair. In vitro matured oocytes were parthenogenetically activated (PA) and cultured in synthetic oviduct fluid medium. Early- and late-cleaved embryos were fixed at 36, 50, 60, 70 and 80 hr after PA to detect the presence of H3K14ac and HMGN2. The rates of nuclear maturation (81.1% vs. 58.7%), early cleavage (46.9% vs. 38.9%), and development to blastocyst stage (34.3% vs. 18.9%) were higher (P,<,0.05) in oocytes derived from large- compared to small follicles. The proportion of positively stained nuclei at 50 and 60 hr after PA was higher for both H3K14ac (27.2% vs. 4.8% and 64.3% vs. 30%) and HMGN2 (47% vs. 21.3% and 60.6% vs. 46%) in early versus late cleaved embryos derived from small- versus large-follicles, respectively. However, the rate of positive nuclei in early-cleaved embryos from small-versus large-follicles was similar for HMGN2 (87% vs. 93%) but lower for H3K14ac (51% vs. 64.4%) at 80 hr after PA. These data suggest that less developmentally competent embryos derived from small follicles had an altered chromatin remodeling process at the early stages of development compared to those derived from large follicles that are more competent to support development to blastocyst stage. Mol. Reprod. Dev. 75: 282,290, 2008. © 2007 Wiley-Liss, Inc. [source] Does CTCF mediate between nuclear organization and gene expression?BIOESSAYS, Issue 1 2010Rolf Ohlsson Abstract The multifunctional zinc-finger protein CCCTC-binding factor (CTCF) is a very strong candidate for the role of coordinating the expression level of coding sequences with their three-dimensional position in the nucleus, apparently responding to a "code" in the DNA itself. Dynamic interactions between chromatin fibers in the context of nuclear architecture have been implicated in various aspects of genome functions. However, the molecular basis of these interactions still remains elusive and is a subject of intense debate. Here we discuss the nature of CTCF-DNA interactions, the CTCF-binding specificity to its binding sites and the relationship between CTCF and chromatin, and we examine data linking CTCF with gene regulation in the three-dimensional nuclear space. We discuss why these features render CTCF a very strong candidate for the role and propose a unifying model, the "CTCF code," explaining the mechanistic basis of how the information encrypted in DNA may be interpreted by CTCF into diverse nuclear functions. [source] Genetic connections of the actin cytoskeleton and beyond,BIOESSAYS, Issue 5 2007Piergiorgio Percipalle Actin is a key protein in numerous cellular functions. One recent study has identified a large set of genes, associated with the actin cytoskeleton, which could be grouped into a wide spectrum of cytoplasmic and nuclear functions, such as protein biosynthesis and gene transcription.1 Deletions of many of the identified genes affected cellular actin organization,1 suggesting a functional link between different actin fractions probably regulated through changes in actin dynamics. The data are very exciting; speculations on the crosstalk between cytoplasmic and nuclear actin fractions in different cellular contexts may help placing the results in perspective to further understand how actin-mediated signalling affects cellular functions, such as gene expression. BioEssays 29:407,411, 2007. © 2007 Wiley Periodicals, Inc. [source] Parathyroid hormone-related protein and its receptors: nuclear functions and roles in the renal and cardiovascular systems, the placental trophoblasts and the pancreatic isletsBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2001Thomas L Clemens The cloning of the so-called ,parathyroid hormone-related protein' (PTHrP) in 1987 was the result of a long quest for the factor which, by mimicking the actions of PTH in bone and kidney, is responsible for the hypercalcemic paraneoplastic syndrome, humoral calcemia of malignancy. PTHrP is distinct from PTH in a number of ways. First, PTHrP is the product of a separate gene. Second, with the exception of a short N-terminal region, the structure of PTHrP is not closely related to that of PTH. Third, in contrast to PTH, PTHrP is a paracrine factor expressed throughout the body. Finally, most of the functions of PTHrP have nothing in common with those of PTH. PTHrP is a poly-hormone which comprises a family of distinct peptide hormones arising from post-translational endoproteolytic cleavage of the initial PTHrP translation products. Mature N-terminal, mid-region and C-terminal secretory forms of PTHrP are thus generated, each of them having their own physiologic functions and probably their own receptors. The type 1 PTHrP receptor, binding both PTH(1-34) and PTHrP(1-36), is the only cloned receptor so far. PTHrP is a PTH-like calciotropic hormone, a myorelaxant, a growth factor and a developmental regulatory molecule. The present review reports recent aspects of PTHrP pharmacology and physiology, including: (a) the identification of new peptides and receptors of the PTH/PTHrP system; (b) the recently discovered nuclear functions of PTHrP and the role of PTHrP as an intracrine regulator of cell growth and cell death; (c) the physiological and developmental actions of PTHrP in the cardiovascular and the renal glomerulo-vascular systems; (d) the role of PTHrP as a regulator of pancreatic beta cell growth and functions, and, (e) the interactions of PTHrP and calcium-sensing receptors for the control of the growth of placental trophoblasts. These new advances have contributed to a better understanding of the pathophysiological role of PTHrP, and will help to identify its therapeutic potential in a number of diseases. British Journal of Pharmacology (2001) 134, 1113,1136; doi:10.1038/sj.bjp.0704378 [source] | |||||||||||||