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EMBRYONIC STEM CELLS/INDUCED PLURIPOTENT STEM CELLS

Characterization of a Novel Ubiquitin-Conjugating Enzyme That Regulates β1,4-Galactosyltransferase-1 in Embryonic Stem Cells

^aThe Center for Cardiovascular Biology and Atherosclerosis Research, Department of Internal Medicine, The University of Texas Medical School at Houston, Houston, Texas, USA;
^bDepartment of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA;
^cHeart Failure and Stem Cell Research Laboratory, The Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas, USA

Key Words. Galactosyltransferase • Ubiquitin-conjugating enzyme • Stem cells • Cell adhesion • Embryoid body

Correspondence: Correspondence: Michael J. Wassler, Ph.D., The Center for Cardiovascular Biology and Atherosclerosis Research, Division of Cardiology, Department of Internal Medicine, The University of Texas Health Science Center at Houston, School of Medicine, 6431 Fannin Street, MSB 1.240, Houston, Texas 77030, USA. Telephone: 713-500-6071; Fax: 713-500-0577; e-mail: Michael.Wassler{at}uth.tmc.edu; or Yong-Jian Geng, M.D., Ph.D., The Center for Cardiovascular Biology and Atherosclerosis Research, Division of Cardiology, Department of Internal Medicine, The University of Texas Health Science Center at Houston, School of Medicine, 6431 Fannin Street, MSB 1.240, Houston, Texas 77030, USA. Telephone: 713-500-6071; Fax: 713-500-0577; e-mail: Yong-Jian.Geng{at}uth.tmc.edu

Received on January 8, 2008; accepted for publication on May 17, 2008.

First published online in STEM CELLS EXPRESS  May 29, 2008.

In this study we identified a novel galactosyltransferase 1-associating protein (GTAP) by cDNA cloning from a murine embryonic cDNA library using the two-hybrid yeast system. GTAP is expressed in early embryonic tissues, as well as in adult tissues with active cell turnover, and belongs to the class III ubiquitin-conjugating (E2) enzyme family. Its COOH-terminal domain contains a consensus sequence for ubiquitin binding shared by all the ubiquitin-conjugating enzymes, whereas its NH₂-terminal domain appears critical for the binding and internalization of cell surface galactosyltransferase 1 (GalT1) in embryonic stem cells through a monensin- and MG132-dependent pathway. We have found that GTAP regulates GalT1-associated, laminin-dependent embryonic cell adhesion and the formation of embryoid bodies. Thus, GTAP functions as an evolutionarily conserved E2 enzyme, which may participate in intercellular adhesion and embryonic development.

Disclosure of potential conflicts of interest is found at the end of this article.