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PMID: 7957052 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia.

The EMBO journal ·Vol. 13 ·No. 20 ·1994-10-17 ·Pages 4831-9

Wadman I, Li J, Bash RO, Forster A, Osada H, Rabbitts TH, Baer R

Abstract

The protein products of proto-oncogenes implicated in T cell acute lymphoblastic leukemia include two distinct families of presumptive transcription factors. RBTN1 and RBTN2 encode highly related proteins that possess cysteine-rich LIM motifs. TAL1, TAL2 and LYL1 encode a unique subgroup of basic helix-loop-helix (bHLH) proteins that share exceptional homology in their bHLH sequences. We have found that RBTN1 and RBTN2 have the ability to interact with each of the leukemogenic bHLH proteins (TAL1, TAL2 and LYL1). These interactions occur in vivo and appear to be mediated by sequences within the LIM and bHLH domains. The LIM-bHLH interactions are highly specific in that RBTN1 and RBTN2 will associate with TAL1, TAL2 and LYL1, but not with other bHLH proteins, including E12, E47, Id1, NHLH1, AP4, MAX, MYC and MyoD1. Moreover, RBTN1 and RBTN2 can interact with TAL1 polypeptides that exist in assembled bHLH heterodimers (e.g. TAL1-E47), suggesting that the RBTN proteins can influence the functional properties of TAL1. Finally, we have identified a subset of leukemia patients that harbor tumor-specific rearrangements of both their RBTN2 and TAL1 genes. Thus, the activated alleles of these genes may promote leukemia cooperatively, perhaps as a result of bHLH-LIM interactions between their protein products.

Related Genes
LYL1 RBTN1 RBTN2 TAL1 TAL2
MeSH Terms
Amino Acid Sequence Gene Rearrangement Helix-Loop-Helix Motifs Humans Leukemia-Lymphoma, Adult T-Cell/genetics Molecular Sequence Data Peptides/metabolism Protein Binding Proto-Oncogene Proteins/genetics,metabolism
Chemicals
Peptides Proto-Oncogene Proteins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Wadman I
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Li J
Bash R O
Forster A
Osada H
Rabbitts T H
Baer R
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1994-10-17
Pages
4831-9
Language
English
Region
England
NLM ID
8208664
PMCID
PMC395422
Subset
IM
Grants
NCI NIH HHS · CA46593 · United States
External Links
PubMed source PMC Full Text View journal details
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