This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a colleague Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Lasorella, A. Articles by Iavarone, A. Search for Related Content PubMed PubMed Citation Articles by Lasorella, A. Articles by Iavarone, A. Social Bookmarking                What's this?

 Previous Article  | Table of Contents |  Next Article 

BIOLOGICAL SCIENCES / DEVELOPMENTAL BIOLOGY
The protein ENH is a cytoplasmic sequestration factor for Id2 in normal and tumor cells from the nervous system

Anna Lasorella, and Antonio Iavarone^*

Institute for Cancer Genetics, Department of Pathology, Pediatrics, and Neurology, Columbia University Medical Center, New York, NY 10032

Communicated by Mario R. Capecchi, University of Utah, Salt Lake City, UT, January 6, 2006 (received for review November 28, 2005)

Id2 is a natural inhibitor of the basic helix–loop–helix transcription factors and the retinoblastoma tumor suppressor protein. Active Id2 prevents differentiation and promotes cell-cycle progression and tumorigenesis in the nervous system. A key event that regulates Id2 activity during differentiation is translocation from the nucleus to the cytoplasm. Here we show that the actin-associated protein enigma homolog (ENH) is a cytoplasmic retention factor for Id2. ENH contains three LIM domains, which bind to the helix–loop–helix domain of Id proteins in vitro and in vivo. ENH is up-regulated during neural differentiation, and its ectopic expression in neuroblastoma cells leads to translocation of Id2 from the nucleus to the cytoplasm, with consequent inactivation of transcriptional and cell-cycle-promoting functions of Id2. Conversely, silencing of ENH by RNA interference prevents cytoplasmic relocation of Id2 in neuroblastoma cells differentiated with retinoic acid. Finally, the differentiated neural crest-derived tumor ganglioneuroblastoma coexpresses Id2 and ENH in the cytoplasm of ganglionic cells. These data indicate that ENH contributes to differentiation of the nervous system through cytoplasmic sequestration of Id2. They also suggest that ENH is a restraining factor of the oncogenic activity of Id proteins in neural tumors.

differentiation | enigma homolog | Id proteins | neural cancer

Conflict of interest statement: No conflicts declared.

*To whom correspondence should be addressed at: Institute for Cancer Genetics, Columbia University Medical Center, 1150 St. Nicholas Avenue, New York, NY 10032. E-mail: ai2102{at}columbia.edu

© 2006 by The National Academy of Sciences of the USA

CiteULike    Complore    Connotea    Del.icio.us    Digg    What's this?

This article has been cited by other articles in HighWire Press-hosted journals:

				C. E. Caldon, A. Swarbrick, C. S.L. Lee, R. L. Sutherland, and E. A. Musgrove The Helix-Loop-Helix Protein Id1 Requires Cyclin D1 to Promote the Proliferation of Mammary Epithelial Cell Acini Cancer Res., April 15, 2008; 68(8): 3026 - 3036. [Abstract] [Full Text] [PDF]

				K. Nishiyama, K. Takaji, Y. Uchijima, Y. Kurihara, T. Asano, M. Yoshimura, H. Ogawa, and H. Kurihara Protein Kinase A-regulated Nucleocytoplasmic Shuttling of Id1 during Angiogenesis J. Biol. Chem., June 8, 2007; 282(23): 17200 - 17209. [Abstract] [Full Text] [PDF]

Current Issue | Archives | Online Submission | Info for Authors | Editorial Board | About Subscribe | Advertise | Contact | Site Map Copyright © 2006 by the National Academy of Sciences