The phosphate group does not act as a docking site for coSMAD, rather the phosphorylation opens up an amino acid stretch allowing interaction. The phosphorylated RSMAD/coSMAD complex enters the nucleus where it binds transcription promoters/cofactors and causes the transcription of DNA. Bone morphogenetic proteins cause the transcription of mRNAs involved in osteogenesis, neurogenesis, and ventral mesoderm specification. TGF betas cause the transcription of mRNAs involved in apoptosis, extracellular matrix neogenesis and immunosuppression. It is also involved in G1 arrest in the cell cycle. Activin causes the transcription of mRNAs involved in gonadal growth, embryo differentiation and placenta formation. Nodal causes the transcription of mRNAs involved in left and right axis specification, mesoderm and endoderm induction. The TGF beta signaling pathway is involved in a wide range of cellular process and subsequently is very heavily regulated. There are a variety of mechanisms where the pathway is modulated either positively or negatively: There are agonists for ligands and R-SMADs; there are decoy receptors; and R-SMADs and receptors are ubiquitinated. Both chordin and noggin are antagonists of BMPs. They bind BMPs preventing the binding of the ligand to the receptor. It has been demonstrated that Chordin and Noggin dorsalize mesoderm. They are both found in the dorsal lip of "Xenopus" and convert otherwise epidermis specified tissue into neural tissue (see neurulation). Noggin plays a key role in cartilage and bone patterning. Mice Noggin-/- have excess cartilage and lacked joint formation. Members of the DAN family of proteins also antagonize TGF beta family members. They include Cerberus, DAN, and Gremlin. These proteins contain nine conserved cysteines which can form disulfide bridges. It is believed that DAN antagonizes GDF5, GDF6 and GDF7. Follistatin inhibits Activin, which it binds. It directly affects follicle-stimulating hormone (FSH) secretion. Follistatin also is implicated in prostate cancers where mutations in its gene may preventing it from acting on activin which has anti-proliferative properties. Lefty is a regulator of TGFβ and is involved in the axis patterning during embryogenesis. It is also a member of the TGF superfamily of proteins.