2016年1月28日 · Here we present the first structure, to our knowledge, of the fully active human HOIP RBR in its transfer complex with an E2~ubiquitin conjugate, which elucidates the intricate nature of RBR E3 ligases. The active HOIP RBR adopts a conformation markedly different from that of auto-inhibited RBRs.

2020年4月3日 · Structural analyses indicated that HOIPINs inhibit the RING-HECT-hybrid reaction in HOIP by modifying the active Cys885, and residues in the C-terminal LDD domain, such as Arg935 and Asp936,...

Here, we show that both LUBAC catalytic activity and LUBAC specificity for linear ubiquitin chain formation are embedded within the RING‐IBR‐RING (RBR) ubiquitin ligase subunit HOIP. Linear ubiquitin chain formation by HOIP proceeds via a two‐step mechanism involving both RING and HECT E3‐type activities.

2016年1月20日 · The first structure of fully active HOIP of the RBR family of RING-type E3 ligases in its transfer complex with an E2~ubiquitin conjugate provides insights into its mechanism of action,...

HOIP is modified by mixed linkage types of linear and Lys‐linked ubiquitin chains in cells, suggesting that additional E3 ligases are involved. A method to generate a ubiquitination mimic of the substrate to directly address the impact of site‐specific ubiquitination, especially by “poly”ubiquitination is not yet established.

In our current study, we implicate the RING Family E3 ligase HOIP in mediating cancer growth and cisplatin resistance via facilitating PTEN degradation. Our study provides a novel regulation mechanism in modulating PTEN stability by HOIP and provides potential targets to re-sensitize chemotherapy resistance in human cancers.

2014年4月4日 · In a focused siRNA screen, using an siRNA library targeting genes involved in ubiquitin and ubiquitin-like signaling, we identified the E3 ubiquitin ligase HOIP as a key regulator of cisplatin-induced genotoxicity. HOIP forms, with SHARPIN and HOIL-1L, the linear ubiquitin assembly complex (LUBAC).

2024年12月20日 · The E3 ligase HOIP is vital for the NF-κB pathway and is implicated in cancer and immunity. However, it remains challenging to achieve high selectivity by directly targeting the conserved catalytic RBR domain of HOIP. Herein, we identified four low-molecular-weight compounds that bind to an uncharac …

2020年12月15日 · HOIP, the catalytic component of the linear ubiquitin chain assembly complex (LUBAC), is a critical regulator of inflammation. However, how HOIP itself is regulated to control inflammatory responses is unclear. Here, we discover that site-specific ubiquitination of K784 within human HOIP promotes tu …

2024年4月6日 · Linear ubiquitination catalyzed by HOIL-1-interacting protein (HOIP), the key component of the linear ubiquitination assembly complex, plays fundamental roles in tissue...