Protein Dimerization Between Lmo2 (Rbtn2) and Tal1 Alters Thymocyte Development and Potentiates T Cell Tumorigenesis in Transgenic Mice

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1996 Mar 1

PMID 8605871

Citations 72

Authors

R C Larson

I Lavenir

T A Larson

R Baer

A J Warren

I Wadman

K Nottage

T H Rabbitts

Affiliations

Soon will be listed here.

Abstract

The LMO2 and TAL1 genes were first identified via chromosomal translocations and later found to encode proteins that interact during normal erythroid development. Some T cell leukaemia patients have chromosomal abnormalities involving both genes, implying that LMO2 and TAL1 act synergistically to promote tumorigenesis after their inappropriate co-expression. To test this hypothesis, transgenic mice were made which co-express Lmo2 and Tal1 genes in T cells. Dimers of Lmo2 and Tal1 proteins were formed in thymocytes of double but not single transgenic mice. Furthermore, thymuses of double transgenic mice were almost completely populated by immature T cells from birth, and these mice develop T cell tumours approximately 3 months earlier than those with only the Lmo2 transgene. Thus interaction between these two proteins can alter T cell development and potentiate tumorigenesis. The data also provide formal proof that TAL1 is an oncogene, apparently acting as a tumour promoter in this system.

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