Faculty Collaboration Database

Posttranslational modification of TEL and TEL/AML1 by SUMO-1 and cell-cycle-dependent assembly into nuclear bodies. Proc Natl Acad Sci U S A 2000 Nov 21;97(24):13281-5

Date

11/15/2000

Pubmed ID

11078523

Pubmed Central ID

PMC27216

DOI

10.1073/pnas.240315897

Scopus ID

2-s2.0-0034700082 (requires institutional sign-in at Scopus site)   104 Citations

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.

Author List

Chakrabarti SR, Sood R, Nandi S, Nucifora G

Author

Rashmi Sood PhD Associate Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
COS Cells
Cell Cycle
Cell Line
Cloning, Molecular
Core Binding Factor Alpha 2 Subunit
DNA-Binding Proteins
Humans
Kidney
Leukemia, Erythroblastic, Acute
Mutagenesis, Site-Directed
Nuclear Proteins
Protein Processing, Post-Translational
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-ets
Recombinant Proteins
Repressor Proteins
SUMO-1 Protein
Saccharomyces cerevisiae
Transcription Factors
Tumor Cells, Cultured
Ubiquitins