Cell Death Dis: Ubiganized modified negative regulator ERR beta promotes the development of breast cancer.

Breast cancer, one of the main causes of cancer death, accounts for 14.3 per cent of all cancer deaths in the less developed countries.
plays an important role in the development of breast cancer.
previous studies have shown that the direct action of estrogen is regulated by estrogen libers (ER).
estrogen-related subjects (ERRs) are highly congenital to ER in protein structure and can mediat transcription of estrogen-induced genes through ERE and ERRE components in the promoter region.
-type ubibin modification (NEDDylation) is the process of binding the ubibinic molecule NEDD8 to the target protein through a three-step enzymatic reaction.
previous studies have shown that the substrate of NEDDylation is the Cullin protein family.
previous studies have shown that expression levels of ERR beta (estrogen-related beta) in breast cancer cells were reduced, while their high levels of expression in breast cancer patients were positively associated with an increase in prognostic and recurrence rates.
the study aims to reveal the molecular mechanisms of lower levels of ERR beta expression in breast cancer.
ERR beta is a key substrate of the SCF complex, and researchers have found that NEDDylation activates the Cullin subkey of the SCF complex, mediates the degradation of ERR beta in breast cancer.
same internal and external source experiments have shown that MLN4924, a NEDDylation-specific small molecule inhibitor, restores the expression level of ERR beta and ultimately weakens the proliferation and migration of breast cancer cells.
further studies have shown that elevated expression of ERR beta can increase the expression levels of its target genes, including tumor suppressor genes p21Cip1/Waf1 and E-calcium adhesion protein (E-cadherin), which can be involved in inhibiting cell proliferation and migration.
interesting is that this tumor suppression of ERR beta does not depend on the expression of ER alpha.
addition, ERR beta is able to increase the expression of the target gene by recruiting the transcription co-activation factor p300 to the promoter region of its target gene.
, the study found that NEDDylation inhibitor MMLN4924 can restore the expression of ERR beta, which may be a potential new strategy for breast cancer treatment.
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