Search Results

Aprataxin localizes to mitochondria and preserves mitochondrial function.

Ataxia with oculomotor apraxia 1 is caused by mutation in the APTX gene, which encodes the DNA strand-break repair protein aprataxin. Aprataxin exhibits homology to the histidine triad superfamily of nucleotide hydrolases and transferases and removes...

Authors: Sykora P, Croteau DL, Bohr VA, Wilson DM 3rd.

Nuclear receptor-induced chromosomal proximity and DNA breaks underlie specific translocations in cancer.

Chromosomal translocations are a hallmark of leukemia/lymphoma and also appear in solid tumors, but the underlying mechanism remains elusive. By establishing a cellular model that mimics the relative frequency of authentic translocation events...

Authors: Lin C, Yang L, Tanasa B, Hutt K, Ju BG, Ohgi K, Zhang J, Rose DW, Fu XD, Glass CK, Rosenfeld MG.

Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size

Myostatin is a negative regulator of skeletal muscle size, previously shown to inhibit muscle cell differentiation. Myostatin requires both Smad2 and Smad3 downstream of the activin receptor II (ActRII)/activin receptor-like kinase (ALK) receptor...

Authors: Trendelenburg AU, Meyer A, Rohner D, Boyle J, Hatakeyama S, Glass DJ.

Disulfiram is a DNA demethylating agent and inhibits prostate cancer cell growth.

BACKGROUND: The clinical success of the nucleoside analogs 5-aza-cytidine (5-azaC) and 5-aza-2'deoxycytidine (5-aza-dC) as DNA methyltransferase (DNMT) inhibitors has spurred interest in the development of non-nucleoside inhibitors with improved...

Authors: Lin J, Haffner MC, Zhang Y, Lee BH, Brennen WN, Britton J, Kachhap SK, Shim JS, Liu JO, Nelson WG,...

Human skeletal muscle drug transporters determine local exposure and toxicity of statins

RATIONALE: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, are important drugs used in the treatment and prevention of cardiovascular disease. Although statins are well tolerated, many patients develop myopathy manifesting...

Authors: Knauer MJ, Urquhart BL, Meyer zu Schwabedissen HE, Schwarz UI, Lemke CJ, Leake BF, Kim RB, Tirona...

Chimeric adenoviral vectors incorporating a fiber of human adenovirus 3 efficiently mediate gene transfer into prostate cancer cells.

BACKGROUND: We have developed a range of adenoviral (Ad) vectors based on human adenovirus serotype 5 (HAdV-5) displaying the fiber shaft and knob domains of species B viruses (HAdV-3, -11, or -35). These species B Ads utilize different cellular...

Authors: Murakami M, Ugai H, Belousova N, Pereboev A, Dent P, Fisher PB, Everts M, Curiel DT.

Promoter DNA Methylation Patterns of Differentiated Cells Are Largely Programmed at the Progenitor Stage

Mesenchymal stem cells (MSCs) isolated from various tissues share common phenotypic and functional properties. However, intrinsic molecular evidence supporting these observations has been lacking. Here, we unravel overlapping genome-wide promoter DNA...

Authors: Sørensen AL, Jacobsen BM, Reiner AH, Andersen IS, Collas P

Adenovirus-mediated sensitization to the cytotoxic drugs docetaxel and mitoxantrone is dependent on regulatory domains in the E1ACR1 gene-region.

Oncolytic adenoviruses have shown promising efficacy in clinical trials targeting prostate cancers that frequently develop resistance to all current therapies. The replication-selective mutants Ad?? and dl922-947, defective in pRb-binding, have been...

Authors: Miranda E, Maya Pineda H, Öberg D, Cherubini G, Garate Z, Lemoine NR, Halldén G

HspB2/Myotonic Dystrophy Protein Kinase Binding Protein (MKBP) as a Novel Molecular Chaperone: Structural and Functional Aspects

The small heat shock protein, human HspB2, also known as Myotonic Dystrophy Kinase Binding Protein (MKBP), specifically associates with and activates Myotonic Dystrophy Protein Kinase (DMPK), a serine/threonine protein kinase that plays an important...

Authors: Prabhu S, Raman B, Ramakrishna T, Rao ChM

Improved potency and selectivity of an oncolytic E1ACR2 and E1B19K deleted adenoviral mutant in prostate and pancreatic cancers.

PURPOSE: Replication-selective oncolytic adenoviruses are a promising class of tumor-targeting agents with proven safety in hundreds of patients. However, clinical responses have been limited and viral mutants with higher potency are needed. Here, we...

Authors: Oberg D, Yanover E, Adam V, Sweeney K, Costas C, Lemoine NR, Halldén G.

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