摘要:
The invention provides methods of identifying an E-SYT2 modulator. The methods may comprise providing a cell that expresses E-SYT2; contacting the cell with a candidate chemical entity; and characterizing recruitment of at least one of Carma1, BcllO, NEMO, and PKC9 to the immunological synapse (IS). The invention also provides E-SYT2 modulators, including inhibitors, identified using the disclosed methods. The invention provides methods of inhibiting NF-κB activity in a cell comprising contacting the cell with an E-SYT2 inhibitor. The invention provides methods comprising providing a sample from a patient suspected of having or at risk of having a MALT-lymphoma or an ABC-DLBCL-lymphoma; and screening the sample to identify the presence and/or absence of a gain of function E-Syt2 mutation in the sample. The invention also provides genetically modified mammals comprising one or two loss of function alleles of E-Syt2.