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Calgary, Canada

Smith C.L.,University of Massachusetts Medical School | Matheson T.D.,University of Massachusetts Medical School | Trombly D.J.,University of Massachusetts Medical School | Sun X.,University of Massachusetts Medical School | And 5 more authors.
Molecular Biology of the Cell | Year: 2014

Chromatin assembly factor-1 (CAF-1) is a three-subunit protein complex conserved throughout eukaryotes that deposits histones during DNA synthesis. Here we present a novel role for the human p150 subunit in regulating nucleolar macromolecular interactions. Acute depletion of p150 causes redistribution of multiple nucleolar proteins and reduces nucleolar association with several repetitive element-containing loci. Of note, a point mutation in a SUMO-interacting motif (SIM) within p150 abolishes nucleolar associations, whereas PCNA or HP1 interaction sites within p150 are not required for these interactions. In addition, acute depletion of SUMO-2 or the SUMO E2 ligase Ubc9 reduces α-satellite DNA association with nucleoli. The nucleolar functions of p150 are separable from its interactions with the other subunits of the CAF-1 complex because an N-terminal fragment of p150 (p150N) that cannot interact with other CAF-1 subunits is sufficient for maintaining nucleolar chromosome and protein associations. Therefore these data define novel functions for a separable domain of the p150 protein, regulating protein and DNA interactions at the nucleolus. © 2014 Weaver. Source

Mendel D.B.,Med Immune Ltd. | Cherrington J.M.,Zenith Epigenetics | Laird A.D.,Pfizer
Clinical cancer research : an official journal of the American Association for Cancer Research | Year: 2015

The article by Mendel and colleagues, published in the January 1, 2003, issue of Clinical Cancer Research, described their novel preclinical approach to developing a thorough understanding of the exposure-activity relationship for sunitinib, a multitargeted receptor tyrosine kinase inhibitor being developed for oncology therapy. This work successfully set exposure guidelines to identify a biologically active dose in early clinical trials. ©2015 American Association for Cancer Research. Source

Zenith Epigenetics | Date: 2015-06-03

The present disclosure relates to compounds, which are useful for inhibition of BET protein function by binding to bromodomains, and their use in therapy.

Zenith Epigenetics | Entity website

About Zenith Epigenetics Corp. Zenith Epigenetics is aclinical stage biotechnology company with a broad and deep drug discovery platform in epigenetics, developing orally active, small molecules that are selective for inhibition of BET bromodomains ...

Zenith Epigenetics | Entity website

Vice President, Discovery Biology and Pre-Clinical Development Position Summary The Vice President, Discovery Biology and Pre-Clinical Development leads Zenith Epigenetics Biology Department and is responsible for identifying new oncology programs and leading their pre-clinical development through IND. Responsibilities Provide scientific expertise and leadership to discovery and translational biology and pre-clinical development ...

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