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Androgen Receptor in Telomeres DNA and Chromosomes
Androgen receptor (AR) plays a role in maintaining telomere stability in prostate cancer cells, as AR inactivation induces telomere dysfunction within 3 h. Since telomere dysfunction in other systems is known to activate ATM (ataxia telangiectasia mutated)-mediated DNA damage response (DDR) signaling pathways, we investigated the role of ATM-mediated DDR signaling in AR-inactivated prostate cancer cells. Indeed, the induction of telomere dysfunction in cells treated with AR-antagonists (Casodex or MDV3100) or AR-siRNA was associated with a dramatic increase in phosphorylation (activation) of ATM and its downstream effector...
Source: Journal of Biological Chemistry - October 16, 2015 Category: Chemistry Authors: Reddy, V., Wu, M., Ciavattone, N., McKenty, N., Menon, M., Barrack, E. R., Reddy, G. P.-V., Kim, S.-H. Tags: Cell Biology Source Type: research

MELK Decreases Replication Stress Cell Biology
Maternal embryonic leucine zipper kinase (MELK) belongs to the subfamily of AMP-activated Ser/Thr protein kinases. The expression of MELK is very high in glioblastoma-type brain tumors, but it is not clear how this contributes to tumor growth. Here we show that the siRNA-mediated loss of MELK in U87 MG glioblastoma cells causes a G1/S phase cell cycle arrest accompanied by cell death or a senescence-like phenotype that can be rescued by the expression of siRNA-resistant MELK. This cell cycle arrest is mediated by an increased expression of p21WAF1/CIP1, an inhibitor of cyclin-dependent kinases, and is associated with the h...
Source: Journal of Biological Chemistry - August 16, 2013 Category: Chemistry Authors: Kig, C., Beullens, M., Beke, L., Van Eynde, A., Linders, J. T., Brehmer, D., Bollen, M. Tags: Signal Transduction Source Type: research

Nuclear Import of HBXIP Requires Collaboration with c-Fos Gene Regulation
Aberrant nuclear localization of oncogenic transcription factors and coactivators always leads to the development of cancer. We have reported that the oncoprotein hepatitis B X-interacting protein (HBXIP) acts as a novel transcriptional coactivator to promote proliferation and migration of breast cancer cells. However, the mechanism of regulating the nuclear import of HBXIP remains unclear. In the present study, we found that HBXIP interacted with c-Fos through their leucine zipper domains in vitro and in vivo. Interestingly, the leucine zipper mutant of HBXIP (or c-Fos) was unavailable to bind to c-Fos (or HBXIP), resulti...
Source: Journal of Biological Chemistry - June 28, 2013 Category: Chemistry Authors: Zhang, Y., Zhao, Y., Li, H., Li, Y., Cai, X., Shen, Y., Shi, H., Li, L., Liu, Q., Zhang, X., Ye, L. Tags: Cell Biology Source Type: research

Ca2+ and Glu Signaling in FMR1 preCGG Astrocytes Neurobiology
Premutation CGG repeat expansions (55–200 CGG repeats; preCGG) within the fragile X mental retardation 1 (FMR1) gene can cause fragile X-associated tremor/ataxia syndrome. Defects in early neuronal migration and morphology, electrophysiological activity, and mitochondria trafficking have been described in a premutation mouse model, but whether preCGG mutations also affect astrocyte function remains unknown. PreCGG cortical astrocytes (∼170 CGG repeats) displayed 3-fold higher Fmr1 mRNA and 30% lower FMR1 protein (FMRP) when compared with WT. PreCGG astrocytes showed modest reductions in expression of glutamate (Glu) tr...
Source: Journal of Biological Chemistry - May 10, 2013 Category: Chemistry Authors: Cao, Z., Hulsizer, S., Cui, Y., Pretto, D. L., Kim, K. H., Hagerman, P. J., Tassone, F., Pessah, I. N. Tags: Molecular Bases of Disease Source Type: research