MIM/BEG4, a Sonic hedgehog-responsive gene that potentiates Gli-dependent transcription.
Sonic hedgehog (Shh) signaling plays a critical role during development and carcinogenesis. While Gli family members govern the transcriptional output of Shh signaling, little is known how Gli-mediated transcriptional activity is regulated. Here we identify the actin-binding protein Missing in Metastasis (MIM) as a new Shh-responsive gene. Together, Gli1 and MIM recapitulate Shh-mediated epidermal proliferation and invasion in regenerated human skin. MIM is part of a Gli/Suppressor of Fused complex and potentiates Gli-dependent transcription using domains distinct from those used for monomeric actin binding. These data define MIM as both a Shh-responsive gene and a new member of the pathway that modulates Gli responses during growth and tumorigenesis.
Callahan
Christopher A
CA
Program in Epithelial Biology and Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
Ofstad
Tyler
T
Horng
Lily
L
Wang
Jordon K
JK
Zhen
Hanson H
HH
Coulombe
Pierre A
PA
Oro
Anthony E
AE
D000199:Actins / Q000378:metabolism; D000818:Animals; D002455:Cell Division; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D053823:Hedgehog Proteins; D006801:Humans; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D009687:Nuclear Proteins; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012038:Regeneration; D012097:Repressor Proteins / Q000378:metabolism; D012867:Skin / Q000166:cytology* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D016335:Zinc Fingers
D000199:Actins; C400551:GLI1 protein, human; C082593:GLI2 protein, human; C498520:Gli1 protein, mouse; C000618551:Gli2 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D008840:Microfilament Proteins; C473219:Mtss1 protein, mouse; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C509239:SHH protein, human; C490763:Sufu protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2