with  the  proteasome  inhibitor  MG132

revealed    that    proteasomes    also    play

a   significant   role   in   BCL10   degrada-

tion.  As  SQSTM1  interacts  with  pro-

teasomes,    the    simplest    interpretation

of these  data  are  that  SQSTM1  directs

K63-polyubiquitinated  BCL10  to  auto-

phagosomes and proteasomes. There are

also  additional  possibilities,  such  as  the

existence of a parallel pathway of TCR-

dependent    K48-polyubiquitination    of

BCL10,  targeting  some  BCL10  for  pro-

teasomal degradation (Fig. 2). The precise

mechanism  of  TCR-dependent   BCL10

degradation will  require  further  charac-

terization of the requirements for BCL10

proteolysis  under  conditions  of selective

inhibition  of  autophagy  or  proteasome

activity.