Posttranslational modification of TEL and TEL/AML1 by SUMO-1 and cell-cycle-dependent assembly into nuclear bodies

Posttranslational modification of TEL and TEL/AML1 by SUMO-1 and cell-cycle-dependent assembly into nuclear bodies

Department of Medicine, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL 60153

Edited by Janet D. Rowley, University of Chicago Medical Center, Chicago, IL, and approved September 28, 2000 (received for review July 7, 2000)

Abstract

The E-26 transforming specific (ETS)-related gene, TEL, also known as ETV6, encodes a strong transcription repressor that is rearranged in several recurring chromosomal rearrangements associated with leukemia and congenital fibrosarcoma. TEL is a nuclear phosphoprotein that is widely expressed in all normal tissues. TEL contains a DNA-binding domain at the C terminus and a helix–loop–helix domain (also called a pointed domain) at the N terminus. The pointed domain is necessary for homotypic dimerization and for interaction with the ubiquitin-conjugating enzyme UBC9. Here we show that the interaction with UBC9 leads to modification of TEL by conjugating it to SUMO-1. The SUMO-1-modified TEL localizes to cell-cycle-specific nuclear speckles that we named TEL bodies. We also show that the leukemia-associated fusion protein TEL/AML1 is modified by SUMO-1 and found in the TEL bodies, in a pattern quite different from what we observe and report for AML1. Therefore, SUMO-1 modification of TEL could be a critical signal necessary for normal functioning of the protein. In addition, the modification by SUMO-1 of TEL/AML1 could lead to abnormal localization of the fusion protein, which could have consequences that include contribution to neoplastic transformation.

Footnotes

↵ * To whom reprint requests should be addressed at: Department of Medicine, Loyola University Medical Center, Cardinal Bernardin Cancer Center, 2160 South First Avenue, Maywood, IL 60153. E-mail: gnucifo{at}luc.edu.
This paper was submitted directly (Track II) to the PNAS office.
Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.240315897.
Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.240315897
Abbreviations:

HLH,

helix–loop–helix;

HA,

hemagglutinin