Protein complex formation between Msx1 and Lhx2 homeoproteins is incompatible with DNA binding activity.
Msx genes encode a family of homeoproteins that function as transcription repressors through protein-protein interactions. Here we show that Lhx2, a LIM-type homeoprotein, is a protein partner for Msx1 in vitro and in cellular extracts. The interaction between Msx1 and Lhx2 is mediated through the homeodomain-containing regions of both proteins. Interestingly, the LIM domains, which serve as protein interaction domains for other partners of Lhx2, are not required for the Msx1-Lhx2 association. We show that Msx1 and Lhx2 form a protein complex in the absence of DNA, and that DNA binding by either protein alone can occur at the expense of protein complex formation. The significance of this protein-protein interaction is underscored by the expression patterns of Msx1 and Lhx2, which are partially overlapping during murine embryogenesis. The description of Lhx2 as a protein partner for Msx1 suggests that the functional specificity of homeoproteins in vivo is determined by a balance between their association with DNA and their protein partners.
Center for Advanced Biotechnology and Medicine, Piscataway, NJ 08854, USA.
A J
AJ
Bendall
D E
DE
Rincón-Limas
J
J
Botas
C
C
Abate-Shen
D000595:Amino Acid Sequence; D000818:Animals; D004247:DNA / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism*; D060850:LIM-Homeodomain Proteins; D018878:Limb Buds / Q000378:metabolism; D051957:MSX1 Transcription Factor; D051379:Mice; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014157:Transcription Factors / Q000378:metabolism*
D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C489784:Lhx2 protein, mouse; D051957:MSX1 Transcription Factor; D014157:Transcription Factors; D004247:DNA