Full Text Journal Articles by
Author Laurence H Hurley


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Nucleolin represses transcription of the androgen receptor gene through a G-quadruplex.

Cindy K Miranti, Sara Moore, Yongeun Kim, Venkateshwar Reddy Chappeta, Kui Wu, Biswanath De, Vijay Gokhale, Laurence H Hurley, Elsa M Reyes-Reyes,

The androgen receptor (AR) is a major driver of prostate cancer development and progression. Men who develop advanced prostate cancer often have long-term cancer control when treated with androgen-deprivation therapies (ADT). Still, their disease inevitably becomes resistant to ADT and progresses to castration-resistant prostate cancer (CRPC). ADT involves potent competitive ... Read more >>

Oncotarget (Oncotarget)
[2020, 11(19):1758-1776]

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Erratum: Nucleolin represses transcription of the androgen receptor gene through a G-quadruplex.

Cindy K Miranti, Sara Moore, Yongeun Kim, Venkateshwar Reddy Chappeta, Kui Wu, Biswanath De, Vijay Gokhale, Laurence H Hurley, Elsa M Reyes-Reyes,

[This corrects the article DOI: 10.18632/oncotarget.27589.]. ...

Oncotarget (Oncotarget)
[2020, 11(26):2586]

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In vitro activity of a G-quadruplex-stabilizing small molecule that synergizes with Navitoclax to induce cytotoxicity in acute myeloid leukemia cells.

Justin J Montoya, Megan A Turnidge, Daniel H Wai, Apurvi R Patel, David W Lee, Vijay Gokhale, Laurence H Hurley, Robert J Arceci, Cynthia Wetmore, David O Azorsa,

BACKGROUND:Acute Myeloid Leukemia (AML) is a malignancy of myeloid precursor cells that arise from genomic alterations in the expression of key growth regulatory genes causing cells to assume an undifferentiated state and continue to proliferate. Recent efforts have focused on developing therapies that target specific protein products of aberrantly expressed ... Read more >>

BMC Cancer (BMC cancer)
[2019, 19(1):1251]

Cited: 1 time

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TGF-β-induced fibrotic stress increases G-quadruplex formation in human fibroblasts.

Priyanka Toshniwal, Michelle Nguyen, Aurore Guédin, Helena Viola, Diwei Ho, Yongeun Kim, Uditi Bhatt, Charles S Bond, Livia Hool, Laurence H Hurley, Jean-Louis Mergny, Mark Fear, Fiona Wood, Swaminathan K Iyer, Nicole M Smith,

Scar formation after wound healing is a major medical problem. A better understanding of the dynamic nuclear architecture of the genome during wound healing could provide insights into the underlying pathophysiology and enable novel therapeutic strategies. Here, we demonstrate that TGF-β-induced fibrotic stress increases formation of the dynamic secondary DNA ... Read more >>

FEBS Lett. (FEBS letters)
[2019, 593(22):3149-3161]

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Intracellular speciation of gold nanorods alters the conformational dynamics of genomic DNA.

Diwei Ho, Jessica A Kretzmann, Marck Norret, Priyanka Toshniwal, Jean-Pierre Veder, Haibo Jiang, Paul Guagliardo, Alaa M Munshi, Reena Chawla, Cameron W Evans, Tristan D Clemons, Michelle Nguyen, Amy L Kretzmann, Amanda J Blythe, Martin Saunders, Michael Archer, Melinda Fitzgerald, Jeffrey A Keelan, Charles S Bond, Matt R Kilburn, Laurence H Hurley, Nicole M Smith, K Swaminathan Iyer,

Gold nanorods are one of the most widely explored inorganic materials in nanomedicine for diagnostics, therapeutics and sensing1. It has been shown that gold nanorods are not cytotoxic and localize within cytoplasmic vesicles following endocytosis, with no nuclear localization2,3, but other studies have reported alterations in gene expression profiles in ... Read more >>

Nat Nanotechnol (Nature nanotechnology)
[2018, 13(12):1148-1153]

Cited: 1 time

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HMGB1 binds to the KRAS promoter G-quadruplex: a new player in oncogene transcriptional regulation?

Jussara Amato, Thushara W Madanayake, Nunzia Iaccarino, Ettore Novellino, Antonio Randazzo, Laurence H Hurley, Bruno Pagano,

This communication reports on a possible distinct role of HMGB1 protein. Biophysical studies revealed that HMGB1 binds and stabilizes the G-quadruplex of the KRAS promoter element that is responsible for most of the transcriptional activity. Biological data showed that inhibition of HMGB1 increases KRAS expression. These results suggest that HMGB1 ... Read more >>

Chem. Commun. (Camb.) (Chemical communications (Cambridge, England))
[2018, 54(68):9442-9445]

Cited: 5 times

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The 3'-end region of the human PDGFR-β core promoter nuclease hypersensitive element forms a mixture of two unique end-insertion G-quadruplexes.

Buket Onel, Megan Carver, Prashansa Agrawal, Laurence H Hurley, Danzhou Yang,

BACKGROUND:While the most stable G-quadruplex formed in the human PDGFR-β promoter nuclease hypersensitive element (NHE) is the 5'-mid G-quadruplex, the 3'-end sequence that contains a 3'-GGA run forms a less stable G-quadruplex. Recently, the 3'-end G-quadruplex was found to be a transcriptional repressor and can be selectively targeted by a ... Read more >>

Biochim Biophys Acta Gen Subj (Biochimica et biophysica acta. General subjects)
[2018, 1862(4):846-854]

Cited: 4 times

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Integrated genomic analyses reveal frequent TERT aberrations in acral melanoma.

Winnie S Liang, William Hendricks, Jeffrey Kiefer, Jessica Schmidt, Shobana Sekar, John Carpten, David W Craig, Jonathan Adkins, Lori Cuyugan, Zarko Manojlovic, Rebecca F Halperin, Adrienne Helland, Sara Nasser, Christophe Legendre, Laurence H Hurley, Karthigayini Sivaprakasam, Douglas B Johnson, Holly Crandall, Klaus J Busam, Victoria Zismann, Valerie Deluca, Jeeyun Lee, Aleksandar Sekulic, Charlotte E Ariyan, Jeffrey Sosman, Jeffrey Trent,

Genomic analyses of cutaneous melanoma (CM) have yielded biological and therapeutic insights, but understanding of non-ultraviolet (UV)-derived CMs remains limited. Deeper analysis of acral lentiginous melanoma (ALM), a rare sun-shielded melanoma subtype associated with worse survival than CM, is needed to delineate non-UV oncogenic mechanisms. We thus performed comprehensive genomic ... Read more >>

Genome Res. (Genome Research)
[2017, 27(4):524-532]

Cited: 18 times

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Simultaneous Drug Targeting of the Promoter MYC G-Quadruplex and BCL2 i-Motif in Diffuse Large B-Cell Lymphoma Delays Tumor Growth.

Samantha Kendrick, Andrea Muranyi, Vijay Gokhale, Laurence H Hurley, Lisa M Rimsza,

Secondary DNA structures are uniquely poised as therapeutic targets due to their molecular switch function in turning gene expression on or off and scaffold-like properties for protein and small molecule interaction. Strategies to alter gene transcription through these structures thus far involve targeting single DNA conformations. Here we investigate the ... Read more >>

J. Med. Chem. (Journal of medicinal chemistry)
[2017, 60(15):6587-6597]

Cited: 12 times

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Correction to "The Dynamic Character of the BCL2 Promoter i-Motif Provides a Mechanism for Modulation of Gene Expression by Compounds That Bind Selectively to the Alternative DNA Hairpin Structure".

Samantha Kendrick, Hyun-Jin Kang, Mohammad P Alam, Manikandadas M Madathil, Prashansa Agrawal, Vijay Gokhale, Danzhou Yang, Sidney M Hecht, Laurence H Hurley,

J. Am. Chem. Soc. (Journal of the American Chemical Society)
[2016, 138(35):11408]

Cited: 0 times

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Identification of G-quadruplexes in long functional RNAs using 7-deazaguanine RNA.

Carika Weldon, Isabelle Behm-Ansmant, Laurence H Hurley, Glenn A Burley, Christiane Branlant, Ian C Eperon, Cyril Dominguez,

RNA G-quadruplex (G4) structures are thought to affect biological processes, including translation and pre-mRNA splicing, but it is not possible at present to demonstrate that they form naturally at specific sequences in long functional RNA molecules. We developed a new strategy, footprinting of long 7-deazaguanine-substituted RNAs (FOLDeR), that allows the ... Read more >>

Nat. Chem. Biol. (Nature chemical biology)
[2017, 13(1):18-20]

Cited: 17 times

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A Pharmacological Chaperone Molecule Induces Cancer Cell Death by Restoring Tertiary DNA Structures in Mutant hTERT Promoters.

Hyun-Jin Kang, Yunxi Cui, Holly Yin, Amy Scheid, William P D Hendricks, Jessica Schmidt, Aleksandar Sekulic, Deming Kong, Jeffrey M Trent, Vijay Gokhale, Hanbin Mao, Laurence H Hurley,

Activation of human telomerase reverse transcriptase (hTERT) is necessary for limitless replication in tumorigenesis. Whereas hTERT is transcriptionally silenced in normal cells, most tumor cells reactivate hTERT expression by alleviating transcriptional repression through diverse genetic and epigenetic mechanisms. Transcription-activating hTERT promoter mutations have been found to occur at high frequencies ... Read more >>

J. Am. Chem. Soc. (Journal of the American Chemical Society)
[2016, 138(41):13673-13692]

Cited: 13 times

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DNA structure: Visualizing the quadruplex.

Adam Siddiqui-Jain, Laurence H Hurley,

Nat Chem (Nature chemistry)
[2013, 5(3):153-155]

Cited: 8 times

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Anticancer activity and cellular repression of c-MYC by the G-quadruplex-stabilizing 11-piperazinylquindoline is not dependent on direct targeting of the G-quadruplex in the c-MYC promoter.

Peda V L Boddupally, Seongmin Hahn, Cristina Beman, Biswanath De, Tracy A Brooks, Vijay Gokhale, Laurence H Hurley,

This G-rich region of the c-MYC promoter has been shown to form a G-quadruplex structure that acts as a silencer element for c-MYC transcriptional control. In the present work, we have synthesized a series of 11-substituted quindoline analogues as c-MYC G-quadruplex-stabilizing compounds, and the cell-free and in vitro activity of ... Read more >>

J. Med. Chem. (Journal of medicinal chemistry)
[2012, 55(13):6076-6086]

Cited: 40 times

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Tertiary DNA structure in the single-stranded hTERT promoter fragment unfolds and refolds by parallel pathways via cooperative or sequential events.

Zhongbo Yu, Vanessa Gaerig, Yunxi Cui, HyunJin Kang, Vijay Gokhale, Yuan Zhao, Laurence H Hurley, Hanbin Mao,

The discovery of G-quadruplexes and other DNA secondary elements has increased the structural diversity of DNA well beyond the ubiquitous double helix. However, it remains to be determined whether tertiary interactions can take place in a DNA complex that contains more than one secondary structure. Using a new data analysis ... Read more >>

J. Am. Chem. Soc. (Journal of the American Chemical Society)
[2012, 134(11):5157-5164]

Cited: 28 times

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Gary S Nichol, Peda V L Boddupally, Biswanath De, Laurence H Hurley,

In the title compound, C(22)H(24)N(4)O, the aromatic moiety is essentially planar (r.m.s. deviation of a least-squares plane fitted through all non-H atoms = 0.0386 Å) and is rotated by 89.98 (4)° from the piperazine ring, which adopts the expected chair conformation. The propanol chain is not fully extended away from the piperazine ... Read more >>

Acta Crystallogr Sect E Struct Rep Online (Acta crystallographica. Section E, Structure reports online)
[2011, 67(Pt 12):o3465-6]

Cited: 0 times

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The vitamin E analog, alpha-tocopheryloxyacetic acid enhances the anti-tumor activity of trastuzumab against HER2/neu-expressing breast cancer.

Tobias Hahn, Deborah J Bradley-Dunlop, Laurence H Hurley, Daniel Von-Hoff, Stephen Gately, Disis L Mary, Hailing Lu, Manuel L Penichet, David G Besselsen, Brook B Cole, Tanisha Meeuwsen, Edwin Walker, Emmanuel T Akporiaye,

HER2/neu is an oncogene that facilitates neoplastic transformation due to its ability to transduce growth signals in a ligand-independent manner, is over-expressed in 20-30% of human breast cancers correlating with aggressive disease and has been successfully targeted with trastuzumab (Herceptin®). Because trastuzumab alone achieves only a 15-30% response rate, it ... Read more >>

BMC Cancer (BMC cancer)
[2011, 11:471]

Cited: 12 times

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The C-terminus of nucleolin promotes the formation of the c-MYC G-quadruplex and inhibits c-MYC promoter activity.

Verónica González, Laurence H Hurley,

Nucleolin, the most abundant nucleolar phosphoprotein of eukaryotic cells, is known primarily for its role in ribosome biogenesis and cell proliferation. It is, however, a multifunctional protein that, depending on the cellular context, can drive either cell proliferation or apoptosis. Our laboratory recently demonstrated that nucleolin can function as a ... Read more >>

Biochemistry (Biochemistry)
[2010, 49(45):9706-9714]

Cited: 48 times

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Molecular cloning of the human platelet-derived growth factor receptor beta (PDGFR-beta) promoter and drug targeting of the G-quadruplex-forming region to repress PDGFR-beta expression.

Yong Qin, Jessica S Fortin, Denise Tye, Mary Gleason-Guzman, Tracy A Brooks, Laurence H Hurley,

To understand the mechanisms controlling platelet-derived growth factor receptor beta (PDGFR-beta) expression in malignancies, we have cloned and characterized the first functional promoter of the human PDGFR-beta gene, which has been confirmed by luciferase reporter gene assays. The transcription initiation sites were mapped by primer extension. Promoter deletion experiments demonstrate ... Read more >>

Biochemistry (Biochemistry)
[2010, 49(19):4208-4219]

Cited: 39 times

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The c-MYC NHE III(1): function and regulation.

Verónica González, Laurence H Hurley,

c-MYC is an important regulator of a wide array of cellular processes necessary for normal cell growth and differentiation, and its dysregulation is one of the hallmarks of many cancers. Consequently, understanding c-MYC transcriptional activation is critical for understanding developmental and cancer biology, as well as for the development of ... Read more >>

Annu. Rev. Pharmacol. Toxicol. (Annual review of pharmacology and toxicology)
[2010, 50:111-129]

Cited: 71 times

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The role of supercoiling in transcriptional control of MYC and its importance in molecular therapeutics.

Tracy A Brooks, Laurence H Hurley,

MYC is deregulated in most tumour types, but an effective means to selectively target its aberrant expression is not yet available. Supercoiling that is induced by transcription has been demonstrated to have dynamic effects on DNA in the MYC promoter element: it converts duplex DNA to non-duplex DNA structures, even ... Read more >>

Nat. Rev. Cancer (Nature reviews. Cancer)
[2009, 9(12):849-861]

Cited: 130 times

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The i-motif in the bcl-2 P1 promoter forms an unexpectedly stable structure with a unique 8:5:7 loop folding pattern.

Samantha Kendrick, Yoshitsugu Akiyama, Sidney M Hecht, Laurence H Hurley,

Transcriptional regulation of the bcl-2 proto-oncogene is highly complex, with the majority of transcription driven by the P1 promoter site and the interaction of multiple regulatory proteins. A guanine- and cytosine-rich (GC-rich) region directly upstream of the P1 site has been shown to be integral to bcl-2 promoter activity, as ... Read more >>

J. Am. Chem. Soc. (Journal of the American Chemical Society)
[2009, 131(48):17667-17676]

Cited: 58 times

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I-motif structures formed in the human c-MYC promoter are highly dynamic--insights into sequence redundancy and I-motif stability.

Jixun Dai, Emmanuel Hatzakis, Laurence H Hurley, Danzhou Yang,

The GC-rich nuclease hypersensitivity element III1 (NHE III1) of the c-MYC promoter largely controls the transcriptional activity of the c-MYC oncogene. The C-rich strand in this region can form I-motif DNA secondary structures. We determined the folding pattern of the major I-motif formed in the NHE III1, which can be ... Read more >>

PLoS ONE (PloS one)
[2010, 5(7):e11647]

Cited: 26 times

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The design, synthesis, and evaluation of 8 hybrid DFG-out allosteric kinase inhibitors: a structural analysis of the binding interactions of Gleevec, Nexavar, and BIRB-796.

Justin Dietrich, Christopher Hulme, Laurence H Hurley,

The majority of kinase inhibitors developed to date are competitive inhibitors that target the ATP binding site; however, recent crystal structures of Gleevec (imatinib mesylate, STI571, PDB: 1IEP), Nexavar (Sorafenib tosylate, BAY 43-9006, PDB: 1UWJ), and BIRB-796 (PDB: 1KV2) have revealed a secondary binding site adjacent to the ATP binding ... Read more >>

Bioorg. Med. Chem. (Bioorganic & medicinal chemistry)
[2010, 18(15):5738-5748]

Cited: 37 times

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Formation of a unique end-to-end stacked pair of G-quadruplexes in the hTERT core promoter with implications for inhibition of telomerase by G-quadruplex-interactive ligands.

SunMi L Palumbo, Scot W Ebbinghaus, Laurence H Hurley,

The hTERT core promoter contains a G-rich region of 12 consecutive G-tracts, embracing 3 Sp1 binding sites, and has the potential to form multiple G-quadruplexes. From the 12 runs of guanines, 9 putative hTERT G-quadruplex-forming sequences were selected to assay for G-quadruplex formation and stability using circular dichroism and a ... Read more >>

J. Am. Chem. Soc. (Journal of the American Chemical Society)
[2009, 131(31):10878-10891]

Cited: 100 times

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