| 2016 |
RCHY1 (PIRH2) physically interacts with the SARS-CoV SARS-unique domain (SUD) subdomains 389-652 (SUD-NM) via RCHY1 residues 95-144. Association with SUD increases the stability of RCHY1 and augments RCHY1-mediated ubiquitination and degradation of p53, thereby antagonizing p53-dependent antiviral innate immunity. Similarly, papain-like proteases (PLpro) from SARS-CoV, MERS-CoV, and HCoV-NL63 physically interact with and stabilize RCHY1, triggering degradation of endogenous p53. CAMK2D binds SUD and normally influences RCHY1 stability by phosphorylation, but SUD does not regulate RCHY1 phosphorylation via CAMK2D. |
Co-immunoprecipitation, domain-mapping deletion constructs, in vivo ubiquitination assay, p53 degradation assays, phosphorylation analysis |
Proceedings of the National Academy of Sciences of the United States of America |
High |
27519799
|
| 2013 |
Hoxa2 interacts with RCHY1 (PIRH2) and promotes its proteasomal degradation in an ubiquitin-independent manner. Hoxa2 also interacts with 20S proteasome subunits. Hoxa2-mediated RCHY1 degradation alters RCHY1-mediated ubiquitination of p53, leading to p53 stabilization. |
Co-immunoprecipitation, ectopic expression/knockdown with protein level readout, ubiquitination assays, proteasome inhibitor experiments |
PloS one |
Medium |
24244684
|
| 2015 |
The Hoxa2-mediated degradation of RCHY1 involves both the 19S and 20S proteasome complexes and requires the Hoxa2 homeodomain and C-terminal moiety. The homeodomain is necessary but not sufficient for RCHY1 degradation. All tested Hox proteins interact with RCHY1 via the homeodomain, but only a subset can induce RCHY1 degradation. This interaction and functional consequence is evolutionarily conserved among vertebrates. |
Deletion mutagenesis, proteasome complex interaction assays, co-immunoprecipitation with multiple Hox protein variants, cross-species conservation analysis |
PloS one |
Medium |
26496426
|
| 2019 |
RCHY1 directly interacts with HDAC2 and negatively regulates HDAC2 protein levels via its E3 ubiquitin ligase RING domain activity. Ectopic expression of wild-type RCHY1 decreased HDAC2 levels in cancer cells regardless of p53 status, while RING-domain mutant RCHY1 did not, and RCHY1 knockdown increased HDAC2 levels. |
Co-immunoprecipitation, ectopic expression and knockdown, RING-domain mutant analysis, protein level measurement across p53 wild-type, mutant, and null cell lines |
Biochemical and biophysical research communications |
Medium |
31630802
|
| 2024 |
RCHY1 acts as an E3 ubiquitin ligase required for K63-linked ubiquitination of melanosomes. RCHY1 knockdown inhibited melanosome ubiquitination, blocked OPTN translocation to melanosomes (which requires ubiquitin-binding), prevented TBK1 activation and TBK1-mediated S187 OPTN phosphorylation, and abolished melanosome degradation. RCHY1 thus confers cargo selectivity in melanophagy upstream of the OPTN-TBK1 autophagy receptor axis. |
siRNA knockdown, K63-linked ubiquitination assay, immunofluorescence localization of OPTN to melanosomes, TBK1 phosphorylation assay, melanosome degradation quantification in B16F10 cells |
Proceedings of the National Academy of Sciences of the United States of America |
High |
38536750
|
| 2024 |
RCHY1 promotes autophagic flux by facilitating autophagosome-lysosome fusion. Loss of Rchy1 in Drosophila larval midgut cells impaired autophagosome-lysosome fusion and led to accumulation of amphisomes. Depletion of RCHY1 in human HeLa cells also disrupted autophagic flux and reduced autolysosome formation, demonstrating evolutionary conservation of this function. |
Genetic screen in Drosophila, loss-of-function (Rchy1 knockdown/knockout), siRNA in HeLa cells, autophagosome-lysosome fusion assay, autophagy flux assays |
Cell death discovery |
Medium |
41986295
|
| 2022 |
PHB2 (prohibitin 2) upregulates RCHY1, which in turn mediates ubiquitination and degradation of p53 and p21 to promote cell proliferation. DHA downregulates PHB2 in a ubiquitylation-dependent manner and subsequently blocks PHB2-induced RCHY1 upregulation and p53/p21 downregulation. RCHY1 is required for PHB2 to exert its tumor-promoting role. |
Overexpression and knockdown of PHB2 and RCHY1, ubiquitination assays, in vitro and in vivo proliferation assays, protein level analysis |
Molecular carcinogenesis |
Medium |
36342357
|
| 2026 |
Gorab knockout in mouse dermal fibroblasts impairs RCHY1-mediated ubiquitination of P53, leading to P53 accumulation, increased HDAC2 levels, reduced histone acetylation, and downregulation of extracellular matrix proteins, promoting accelerated skin aging. |
Conditional knockout mouse model, protein ubiquitination assay, Western blot for P53/P21/P16/HDAC2/histone acetylation, ECM protein analysis |
Animal models and experimental medicine |
Low |
41869872
|
| 2026 |
LINC00839 destabilizes RCHY1 mRNA through recruitment of UPF1, consequently inhibiting RCHY1-mediated ubiquitination and degradation of DJ-1 protein. RCHY1 depletion neutralized the effect of LINC00839 knockdown on ferroptosis, placing RCHY1 downstream of the LINC00839/UPF1 axis as the E3 ligase responsible for DJ-1 ubiquitination and degradation. |
LINC00839 and RCHY1 knockdown/overexpression, mRNA stability assays, ubiquitination assay for DJ-1, epistasis by rescue experiments, in vivo tumor growth assay |
NPJ precision oncology |
Low |
42135459
|