LLL12 binds to the phosphorylated tyrosine on STAT3 monomers, blocking dimerization and subsequent translocation into the nucleus, abrogating its function as a transcription factor.
Thus, blocking dimerization reduces aggregation and the ensuing peptide toxicity [4].
Interestingly, the STAT3 small molecule inhibitor STA-21, the compound from which LLL3 was derived, was found to act in a similar manner, preventing STAT3 activity by blocking dimerization, translocation into the nucleus, and execution of its signaling pathway in breast cancer cells at roughly the same concentration [ 27].
What is not clear from these studies, however, is whether blocking dimerization abolishes the potential for IKK2 to become active or whether it simply decreases the effective IKK2 concentration and consequently the probability of trans autophosphorylation.
The authors suggest that this monoclonal antibody may function by blocking dimerization of ALK receptors, since stimulation with activating antibodies is abrogated by the inhibitory antibody.
Human Cdc37 (preventsveN-terminalinal dimerization by binding between the N-terminal domains of Hsp90, interacting with the ATP lids themselves, thus physically blocking dimerization [29].
Perjeta is another antibody designed to block dimerization of the HER2 receptor in breast cancer and was approved by the U.S. Food and Drug Administration in 2012.
Although P27 was rationally designed to block dimerization of the mature HIV-1 protease, the effects of P27 on HIV-1 replication may be related to partial inhibition of Gag-Pol processing leading to a disruption in virus release.
Binding of the neutralizing antibody to the second receptor molecule, in this case VEGFR3, may block dimerization either by steric hindrance or by locking the conformation of VEGFR3 in a state incompatible with dimerization.
To investigate the impact of CD146 dimerization on the downstream signal transduction of PDGFRβ in pericytes, we transfected 10T1/2 cells with Cd146/C454A or Cd146/C501A to block dimerization of mice CD146.
