[Yuan J, Cole MD] No mutations known. Related to vertebrate MAD transcription factor, MDL-1 can form DNA-binding heterodimer with MXL-1 in vitro. mdl-1::GFP expression strongest in intestinal cells. Predicted gene R03E9.1.
mdl-1 encodes a basic helix-loop-helix (bHLH) protein similar to the vertebrate MAD transcriptional regulators; in vitro, MDL-1 can heterodimerize, and bind an E-box DNA sequence, with MXL-1, a C. elegans MAX-like bHLH protein; when expressed in rat embryonic fibroblasts, MDL-1 is able to suppress c-MYC/RAS-induced cell transformation, in a manner dependent upon an intact, predicted SIN3 interaction domain; mdl-1::gfp promoter fusions are expressed in a number of different tissues, including the posterior intestine, anterior and ventral cord neurons, pharyngeal and body wall muscles, somatic gonad precursors, and hypodermal cells; yeast one-hybrid and ChIP experiments indicate that DAF-3/Smad can bind the mdl-1 promoter; in addition, mdl-1 pharyngeal expression is specifically increased in daf-3(RNAi) animals, suggesting that DAF-3 directly negatively regulates mdl-1 transcription in pharyngeal tissue during dauer formation.
Enables protein heterodimerization activity. Contributes to sequence-specific DNA binding activity. Involved in determination of adult lifespan and regulation of cell differentiation. Located in nucleus. Part of transcription regulator complex. Expressed in body wall musculature; neurons; pharynx; and somatic nervous system. Used to study Parkinson's disease. Human ortholog(s) of this gene implicated in neurofibrosarcoma and prostate cancer. Is an ortholog of human MXI1 (MAX interactor 1, dimerization protein).
Inferred by orthology to human genes with DO annotation (HGNC:7534)
Disease_relevance
mdl-1 encodes a bHLH (basic-helix-loop-helix) protein similar to the vertebrate MAD transcriptional regulators; mdl-1 is a candidate target gene for the small non-coding RNAs mir-64 and mir-65, and is found to be over-expressed in an transgenic elegans model for Parkinson''s disease, expressing human A53T alpha-synuclein, as well as in mir-64/mir-65 knock-out animals; mir-64 and mir-65 are co-underexpressed in the same model, suggesting a role for all of these genes in disease pathogenesis.
Map position created from combination of previous interpolated map position (based on known location of sequence) and allele information. Therefore this is not a genetic map position based on recombination frequencies or genetic experiments. This was done on advice of the CGC.