SMAD5 [3H9]

SMAD5, MAD homolog 5, Mothers against DPP homolog 5, JV5-1, SMAD family member 5 encoded by the gene named SMAD5 or MADH5 is a transcriptional cofactor activated by BMP type 1 receptor kinase and like other SMAD family members SMAD5 belongs to the larger TGFbeta superfamily of signaling modulators. SMAD5 forms complexes with SMAD4 when phosphorylated by BMPR1 and migrates to the nucleus. In the absence of phosphorylation, SMAD5 is cytoplasmically localized. SMAD5 levels are regulated via ubiquitin mediated proteolysis facilitated by the E3 ligase SMURF1. SMAD5 is involved in many developmental pathways, including in hematopoietic cells, where SMAD5 activity is involved in the inhibition of the proliferation of hematopoietic progenitor cells. More recent research has shown SMAD5 to be involved in many other pathways too, for instance homozygous mutants die early in development and display a variable phenotype. Moreover, SMAD5 is critical for proper granule cell development in the cerebellum. Finally, because SMAD5 belongs to the TGFbeta family whose normal function is usually growth suppression, SMAD5 is often mutated in many cancers and its expression is associated with many forms of cancers in a similar fashion to that of its other family members.