Jk. Leung et al., MRG15 activates the B-myb promoter through formation of a nuclear complex with the retinoblastoma protein and the novel protein PAM14, J BIOL CHEM, 276(42), 2001, pp. 39171-39178
The MORF4-Related Gene on chromosome 15 (MRG15) is a member of a novel fami
ly of genes originally identified in studies to reveal cell senescence-indu
cing factors. MRG15 contains several predicted protein motifs, including a
nuclear localization signal, a helix-loop-helix region, a leucine zipper, a
nd a chromodomain. These motifs are commonly associated with transcription
factors, suggesting that MRG15 may likewise function as a transcriptional r
egulator. To examine the potential function(s) of MRG15, we sought to ident
ify cellular factors associated with this MRG family member. In this regard
, we have found that both the retinoblastoma tumor suppressor (Rb) and a no
vel nuclear protein PAM14 (Protein Associated with MRG, 14 kDa) specificall
y associate with MRG15. We have further demonstrated that these interaction
s require the helix-loop-helix and leucine zipper domains of MRG15. Interes
tingly we have found all three proteins present in a multiprotein complex,
suggesting that at least some of their functions may be interdependent. Alt
hough the functions of PAM14 have yet to be elucidated, Rb has several well
characterized activities, including repression of E2F-activated promoters
such as that of B-myb. Significantly we have demonstrated that MRG15 blocks
the Rb-induced repression of this promoter, leading to B-myb promoter acti
vation. Collectively these results suggest that MRG15 regulates transcripti
on through interactions with a cellular protein complex containing Rb and P
AM14.