描述：
Dkk3, also known as REIC (Reduced Expansion in Immortalized Cells), is one of four
numbered members of the Dickkopf family of Wnt antagonists. Dkk3 is a secreted
monomer expressed in many normal human tissues, most strongly in heart, brain and
spinal cord , and during early embryonic development in the mouse. Nglycosylation
at up to four sites preceding or between two conserved cysteinerich motifs results in
expression of a 45 65 kDa glycoprotein. The cysteinerich motifs contain 10 cysteines
each, with prokineticin and colipase families containing sequences similar to those of
the second motif. Human Dkk3 shows 82%, 88%, 85% and 53% amino acid (aa) identity
with mouse, bovine, canine and chick Dkk3, respectively, and 37 45% aa identity with
other human Dkk family members. Several lines of evidence implicate Dkk3 as a negative
growth regulator. Dkk3 is downregulated in many tumors as compared to normal cells,
sometimes by loss of heterozygosity. Downregulation by CpG hypermethylation in acute
lymphoblastic leukemia is correlated with faster progression and shorter survival. Release
of cultured cells from serum starvation results in downregulation of Dkk3 in late G1 phase
of the cell cycle. Overexpression of Dkk3 results in tumor celllinespecific growth inhibition,
induction of apoptosis, and decreased tumorigenicity in nude mice. The prototype Dickkopf
member, Dkk1, antagonizes Wnt family signaling by binding to Wnt receptors LRP5 and
LRP6 (lowdensity lipoprotein receptorrelated proteins) and promoting their internalization.
Results are less straightforward for Dkk3, where some studies show binding to LRP5/6 while
others do not. These effects appear to be dependent on the cells and conditions used.
原厂资料：
Dkk3, also known as REIC (Reduced Expansion in Immortalized Cells), is one of four
numbered members of the Dickkopf family of Wnt antagonists. Dkk3 is a secreted
monomer expressed in many normal human tissues, most strongly in heart, brain and
spinal cord , and during early embryonic development in the mouse. Nglycosylation
at up to four sites preceding or between two conserved cysteinerich motifs results in
expression of a 45 65 kDa glycoprotein. The cysteinerich motifs contain 10 cysteines
each, with prokineticin and colipase families containing sequences similar to those of
the second motif. Human Dkk3 shows 82%, 88%, 85% and 53% amino acid (aa) identity
with mouse, bovine, canine and chick Dkk3, respectively, and 37 45% aa identity with
other human Dkk family members. Several lines of evidence implicate Dkk3 as a negative
growth regulator. Dkk3 is downregulated in many tumors as compared to normal cells,
sometimes by loss of heterozygosity. Downregulation by CpG hypermethylation in acute
lymphoblastic leukemia is correlated with faster progression and shorter survival. Release
of cultured cells from serum starvation results in downregulation of Dkk3 in late G1 phase
of the cell cycle. Overexpression of Dkk3 results in tumor celllinespecific growth inhibition,
induction of apoptosis, and decreased tumorigenicity in nude mice. The prototype Dickkopf
member, Dkk1, antagonizes Wnt family signaling by binding to Wnt receptors LRP5 and
LRP6 (lowdensity lipoprotein receptorrelated proteins) and promoting their internalization.
Results are less straightforward for Dkk3, where some studies show binding to LRP5/6 while
others do not. These effects appear to be dependent on the cells and conditions used.
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