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

Isobel Wadman, Jinxing Li, Robert O. Bash, Alan Forster, Hiro Osada, Terence H. Rabbitts, Richard Baer

Research output: Contribution to journalArticle

204 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)4831-4839
Number of pages9
JournalEMBO Journal
Volume13
Issue number20
StatePublished - 1994

Fingerprint

T-Cell Leukemia
T-cells
Proteins
Proto-Oncogene Proteins
Leukemia
Helix-Loop-Helix Motifs
Transcription Factor 3
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Genes
Cysteine
Transcription Factors
Alleles
Ports and harbors
Peptides
Tumors
Neoplasms

Keywords

  • Leukemia
  • Oncogene
  • Transcription factor

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

Wadman, I., Li, J., Bash, R. O., Forster, A., Osada, H., Rabbitts, T. H., & Baer, R. (1994). Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia. EMBO Journal, 13(20), 4831-4839.

Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia. / Wadman, Isobel; Li, Jinxing; Bash, Robert O.; Forster, Alan; Osada, Hiro; Rabbitts, Terence H.; Baer, Richard.

In: EMBO Journal, Vol. 13, No. 20, 1994, p. 4831-4839.

Research output: Contribution to journalArticle

Wadman, I, Li, J, Bash, RO, Forster, A, Osada, H, Rabbitts, TH & Baer, R 1994, 'Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia', EMBO Journal, vol. 13, no. 20, pp. 4831-4839.
Wadman I, Li J, Bash RO, Forster A, Osada H, Rabbitts TH et al. Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia. EMBO Journal. 1994;13(20):4831-4839.
Wadman, Isobel ; Li, Jinxing ; Bash, Robert O. ; Forster, Alan ; Osada, Hiro ; Rabbitts, Terence H. ; Baer, Richard. / Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia. In: EMBO Journal. 1994 ; Vol. 13, No. 20. pp. 4831-4839.
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