Functional diversity of LIM proteins : amino-terminal activation domains in the oncogenic proteins RBTN1 and RBTN2

• The RBTN1 and RBTN2 genes are activated by distinct translocations involving chromosome 11 in some T cell acute leukaemias. The RBTN proteins belong to the LIM family which comprises proteins with one, two or three cysteine-rich LIM domains, sometimes together with homeodomains or protein kinase domains. The RBTN1 and RBTN2 proteins comprise only tandem LIM domains. We report that RBTN1 and RBTN2 proteins are capable of supporting transcriptional transactivation of specific reporter genes in transfection assays. The results, using intact proteins or fusions with the homeodomain of the heterologous protein Isl-1, show that this transcriptional activation ability resides in the NH2-terminal parts of both proteins. The use of yeast assays with RBTN2 shows that RBTN2 forms homodimers and that the NH2-terminal 27 amino acids are sufficient to facilitate transcriptional transactivation. These data expand the functional diversity of the LIM-domain protein family and they augment the previously defined relationship between chromosomal translocations and transcriptional activation.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Hematologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Hematology (hsv//eng)

Nyckelord

Adaptor Proteins, Signal Transducing

Amino Acid Sequence

DNA-Binding Proteins

Humans

LIM Domain Proteins

Metalloproteins

Molecular Sequence Data

Mutagenesis, Site-Directed

Oligodeoxyribonucleotides

Oncogene Proteins

Proto-Oncogene Proteins

Saccharomyces cerevisiae

Structure-Activity Relationship

Trans-Activators

Transcription Factors

Transcriptional Activation

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