摘要: Nanog was identified by its ability to sustain the LIF-independent self-renewal of mouse embryonic stem (ES) cells and
has recently been shown to play a role in reprogramming
adult fibroblasts into pluripotent stem cells. However, little is
known about the structural basis of these remarkable activities of Nanog. We have previously identified an unusually
strong transactivator named CD2 at its C terminus. Here we
demonstrate that CD2 is required for Nanog to mediate ES
cell self-renewal. Furthermore, deletion and point mutation
analysis revealed that CD2 relies on at least seven aromatic
amino acid residues to generate its potent transactivating
activity. A mutant Nanog bearing alanine substitutions for
these seven residues fails to confer LIF-independent self-renewal in mouse ES cells. Substitution of CD2 by the viral
transactivator VP16 gave rise to Nanog-VP16, which is 10
times more active than wild-type Nanog in ES cells. Surprisingly, the expression of Nanog-VP16 in mouse ES cells
induces differentiation and is thus unable to sustain LIF-independent self-renewal for mouse ES cells. Taken together,
our results demonstrate that the CD2 domain of Nanog is a
unique transactivator that utilizes aromatic residues to confer specific activity absolutely required for ES self-renewal.