The core and conserved role of MAL is homeostatic regulation of actin levels.
The transcription cofactor MAL is regulated by free actin levels and thus by actin dynamics. MAL, together with its DNA-binding partner, SRF, is required for invasive cell migration and in experimental metastasis. Although MAL/SRF has many targets, we provide genetic evidence in both Drosophila and human cellular models that actin is the key target that must be regulated by MAL/SRF for invasive cell migration. By regulating MAL/SRF activity, actin protein feeds back on production of actin mRNA to ensure sufficient supply of actin. This constitutes a dedicated homeostatic feedback system that provides a foundation for cellular actin dynamics.
Institute of Molecular and Cell Biology, Singapore 138673, Singapore.
Lara
L
Salvany
Institute of Molecular and Cell Biology, Singapore 138673, Singapore.
Julius
J
Muller
Institute of Molecular and Cell Biology, Singapore 138673, Singapore.
Ernesto
E
Guccione
Institute of Molecular and Cell Biology, Singapore 138673, Singapore.
Pernille
P
Rørth
D000199:Actins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000166:cytology / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006706:Homeostasis; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D026362:Serum Response Factor / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D059467:Transcriptome
D000199:Actins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C431575:MRTFA protein, human; C488977:Mrtf protein, Drosophila; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D026362:Serum Response Factor; D015534:Trans-Activators; D014157:Transcription Factors
actin synthesis; invasive cell migration; transcriptional regulation