Journal of Cell Science & Therapy
Open Access

Study of the RESTUSP37- p27 axis in cell proliferation and differentiation

International Conference & Exhibition on Cell Science & Stem Cell Research

29 Nov - 1 Dec 2011 Philadelphia Airport Marriott, USA

Vidya Gopalakrishnan, Chandramallika Das, Monica Gireud, Pete Taylor, Akanksha Singh, Dean Lee, Kenneth Aldape, Gregory Fuller, Lingyun Ji, Jason Fangusaro, Veena Rajaram, Stewart Goldman and Charles Eberhart

Scientific Tracks Abstracts: J Cell Sci Ther

Abstract :

Medulloblastoma is a malignant pediatric brain tumor. Th ese tumors are characterized by deregulated proliferation and poor neuronal diff erentiation. We previously demonstrated aberrant expression of the RE1 Silencing Transcription Factor (REST) in human medulloblastoma samples. REST is a repressor of neuronal diff erentiation genes, and consistent with this REST expressing tumors fail to undergo neurogenesis. Here, we describe the identifi cation of a novel function for REST in cell proliferation. REST expression in human tumors and in mouse granule cell progenitors (the cells of origin of a subset of medulloblastoma) was associated with lower levels of the cyclin-dependent kinase inhibitor p27. REST repressed the expression of a gene encoding a deubiquitylase USP37. Using genetic and biochemical approaches, we showed complex formation and USP37-dependent deubiquitination and stabilization of p27 in vitro and in vivo . USP37 and p27 expression ere also positively correlated in patient tumors and in the murine cerebellum. Constitutive USP37 expression countered REST-mediated blockade of neuronal diff erentiation and prevented anchorage independent growth of medulloblastoma cells in vitro . In summary, our work has (a) attributed a novel function for REST in the control of cell proliferation (b) established a unique link between REST and p27 (c) identifi ed the deubiquitylase USP37 as a novel REST target (d) and provided the fi rst demonstration of a p27- associated deubiquitylase. Th ese fi ndings have implications for medulloblastoma development

Biography :

Dr. Gopalakrishnan completed her Ph.D from the University of Pittsburgh and her postdoctoral studies from Johns Hopkins University School of Medicine. She is currently an Assistant Professor of Pediatrics and Molecular and Cellular Oncology at the University of Texas MD Anderson Cancer Center. Her research is focused on developing mouse models for pediatric brain tumors, identifying novel molecules for targeted therapeutics and manipulating lineage speci fi cation in stem cells for neuro-regeneration. She has a number of publications in high impact peer-reviewed journals