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Cue Domain-Containing Protein 2

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A protein involved in the ubiquitin-proteasome pathway through degradation of progesterone receptor and estrogen receptor.


Cue Domain-Containing Protein 2 gene is mapped on chromosome 1024.32 containing 9 exons with 226 amino acids that shows an inhibitory effect on endoplasmic reticulum protein level yet no effects occur on STAT5 and p53 proteins. It also involved in 17 beta–estradiol-induced ESR1 degradation that control progesterone levels which is significantly upregulated in breast tumor tissues while lower in low-grade tumors.

Cue Domain-Containing Protein 2 interacts with progesterone and promotes progesterone-induced degradation by ubiquitin-proteasome pathway as well as decreases the sumoylation while promoting ubiquitination on Lys-388 and inhibits the ability of progesterone to stimulate rapid MAPK activity which impairs the effects of progesterone on breast cancer cell growth thereby it provides an important insight in breast cancer proliferation.

Cue Domain-Containing Protein 2 is a key factor in endocrine resistance in breast cancer in which it modulates ER-alpha protein stability through ubiquitin-proteasome pathway. It can interact with progesterone and repress progesterone transactivation thus, serves as a novel negative regulator of progesterone and functions to promote the ubiquitin-dependent degradation.

Gene name: CUEDC2

Protein name: CUE domain-containing protein 2




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