Artigo Acesso aberto Revisado por pares

Modification of ASC1 by UFM1 Is Crucial for ERα Transactivation and Breast Cancer Development

2014; Elsevier BV; Volume: 56; Issue: 2 Linguagem: Inglês

10.1016/j.molcel.2014.08.007

ISSN

1097-4164

Autores

Hee Min Yoo, Sung Hwan Kang, Jae Yeon Kim, Jooeun Lee, Min Woo Seong, Seong Won Lee, Seung Hyeun Ka, Yu‐shin Sou, Masaaki Komatsu, Keiji Tanaka, Soon‐Tae Lee, Dong‐Young Noh, Sung Hee Baek, Young Joo Jeon, Chin Ha Chung,

Tópico(s)

Peptidase Inhibition and Analysis

Resumo

Biological roles for UFM1, a ubiquitin-like protein, are largely unknown, and therefore we screened for targets of ufmylation. Here we show that ufmylation of the nuclear receptor coactivator ASC1 is a key step for ERα transactivation in response to 17β-estradiol (E2). In the absence of E2, the UFM1-specific protease UfSP2 was bound to ASC1, which maintains ASC1 in a nonufmylated state. In the presence of E2, ERα bound ASC1 and displaced UfSP2, leading to ASC1 ufmylation. Polyufmylation of ASC1 enhanced association of p300, SRC1, and ASC1 at promoters of ERα target genes. ASC1 overexpression or UfSP2 knockdown promoted ERα-mediated tumor formation in vivo, which could be abrogated by treatment with the anti-breast cancer drug tamoxifen. In contrast, expression of ufmylation-deficient ASC1 mutant or knockdown of the UFM1-activating E1 enzyme UBA5 prevented tumor growth. These findings establish a role for ASC1 ufmylation in breast cancer development by promoting ERα transactivation.

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