The LIM domain protein LPP is a coactivator for the ETS domain transcription factor PEA3.
PEA3 is a member of a subfamily of ETS domain transcription factors which is regulated by a number of signaling cascades, including the mitogen-activated protein (MAP) kinase pathways. PEA3 activates gene expression and is thought to play an important role in promoting tumor metastasis and also in neuronal development. Here, we have identified the LIM domain protein LPP as a novel coregulatory binding partner for PEA3. LPP has intrinsic transactivation capacity, forms a complex with PEA3, and is found associated with PEA3-regulated promoters. By manipulating LPP levels, we show that it acts to upregulate the transactivation capacity of PEA3. LPP can also functionally interact in a similar manner with the related family member ER81. Thus, we have uncovered a novel nuclear function for the LIM domain protein LPP as a transcriptional coactivator. As LPP continually shuttles between the cell periphery and the nucleus, it represents a potential novel link between cell surface events and changes in gene expression.
Guo
Baoqiang
B
Faculty of Life Sciences, University of Manchester, Michael Smith Bldg., Oxford Road, Manchester M13 9PT, United Kingdom.
Sallis
Rosemary E
RE
Greenall
Amanda
A
Petit
Marleen M R
MM
Jansen
Erik
E
Young
Leonie
L
Van de Ven
Wim J M
WJ
Sharrocks
Andrew D
AD
D001483:Base Sequence; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D060588:LIM Domain Proteins; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C095239:ETV1 protein, human; D060588:LIM Domain Proteins; C103594:LPP protein, human; D034741:RNA, Small Interfering; D015534:Trans-Activators; D014157:Transcription Factors; C065788:transcription factor PEA3; D020781:Matrix Metalloproteinase 1