| 2005 |
WDR12 forms a stable trimeric complex with Pes1 and Bop1 (PeBoW complex) in mammalian cells. WDR12 is required for processing of the 32S precursor rRNA. A dominant-negative mutant of WDR12 blocks rRNA processing and induces reversible cell cycle arrest, triggering p53 accumulation in a p19ARF-independent manner in proliferating but not quiescent cells. |
Co-immunoprecipitation, dominant-negative expression, cell fractionation, rRNA processing assays, p53 accumulation assays |
The Journal of cell biology |
High |
16043514
|
| 2007 |
Bop1 is the integral scaffold of the PeBoW complex: knockdown of Bop1 abolishes copurification of Pes1 with WDR12, while recombinant expression of all three subunits (Pes1, Bop1, WDR12) is sufficient for complex formation. WDR12 nucleolar localization depends on its incorporation into the PeBoW complex. Overexpression of Bop1 inhibits cell proliferation and rRNA processing, and coexpression of WDR12 (but not Pes1) rescues these negative effects. |
Recombinant co-expression, Co-immunoprecipitation, siRNA knockdown, indirect immunofluorescence, cell fractionation, sucrose gradient centrifugation |
Molecular and cellular biology |
High |
17353269
|
| 2005 |
The yeast homologue of WDR12, Ytm1, is present in four consecutive 66S preribosomes and forms a heterotrimeric subcomplex with Erb1 (Bop1 homologue) and Nop7 (Pes1 homologue). Ytm1 binds directly to Erb1; mutations in the WD40 motifs of Ytm1 disrupt Erb1 binding, destabilize the heterotrimer, and delay pre-rRNA processing and nuclear export of preribosomes. |
Affinity purification, co-immunoprecipitation, WD40 domain mutagenesis, pre-rRNA processing assays, sucrose gradient sedimentation |
Molecular and cellular biology |
High |
16287855
|
| 2008 |
In yeast, Ytm1 (WDR12 homologue), Erb1, and Nop7 assemble into preribosomes in an interdependent manner. Specific domains within Ytm1 are necessary for interaction with Erb1 and for recruitment into preribosomes. Overexpression of truncated Ytm1 constructs produces dominant negative effects on growth and ribosome biogenesis, defining interaction and functional domains. |
Truncation mutagenesis, dominant-negative overexpression, affinity purification, co-immunoprecipitation, pre-rRNA processing assays |
Molecular biology of the cell |
High |
18448671
|
| 2015 |
The WD40 beta-propeller domains of Erb1 (Bop1) and Ytm1 (WDR12) interact directly via their beta-propeller domains in a high-affinity, novel binding mode. Crystal structure of the Erb1-Ytm1 heterodimer was solved at 2.67 Å. Structure-based interface mutations that impair the Erb1-Ytm1 interaction do not support yeast growth and cause specific defects in 60S subunit synthesis, demonstrating that an intact Erb1-Ytm1 complex is required for 60S maturation. |
X-ray crystallography (2.67 Å resolution), structure-based mutagenesis, in vitro binding assays, yeast growth assays, ribosome profiling |
Nucleic acids research |
High |
26657628
|
| 2015 |
The WD40 beta-propeller domains of Erb1 and Ytm1 (WDR12 ortholog) interact in a novel high-affinity manner. Crystal structure of the C-terminal Erb1-Ytm1 dimer from Chaetomium thermophilum was solved at 2.1 Å. A point mutation within the interface impairs the interaction, negatively affecting growth and ribosome production in yeast. |
X-ray crystallography (2.1 Å), in vitro binding assays, yeast genetics, ribosome biogenesis assays |
Nucleic acids research |
High |
26476442
|
| 2015 |
The N-terminal ubiquitin-like (UBL) domain of Ytm1/WDR12 is bound by the MIDAS domain of midasin (MDN1/Rea1), the AAA-ATPase required for release of the PeBoW/Nop7-Erb1-Ytm1 complex from preribosomal particles. Crystal structure of the yeast Ytm1 UBL domain was solved at 1.7 Å. Human midasin binds WDR12 through its UBL domain; the interaction requires metal ion coordination by the MIDAS domain, as removal of metal ion or mutation of coordinating residues diminishes binding. Mammalian WDR12 nucleolar localization is dependent on active ribosomal RNA transcription. |
X-ray crystallography (1.7 Å), in vitro binding assays, MIDAS domain mutagenesis (metal coordination mutants), indirect immunofluorescence, rRNA transcription inhibition |
The Journal of biological chemistry |
High |
26601951
|
| 2002 |
Mouse WDR12 protein was shown to bind in vitro to the cytoplasmic domain of Notch1. WDR12 was predicted to contain seven WD repeat units and a nuclear localization signal. The amino-terminal region shows similarity to the Notchless WD repeat protein. |
In vitro binding assay (pull-down), sequence analysis, gene expression studies |
Genomics |
Low |
11827460
|
| 2015 |
WDR12 gene delivery into adult rat hearts decreased cellular proliferation, activated the p38 MAPK/HSP27 pathway, and increased BOP1 protein levels, resulting in deterioration of cardiac function (decreased ejection fraction and fractional shortening). WDR12 protein levels were increased in patients with dilated cardiomyopathy and in rats post-infarction. |
Adenovirus-mediated gene delivery, echocardiography, western blot, immunohistochemistry |
PloS one |
Medium |
25915632
|
| 2021 |
WDR12 silencing in glioma stem-like cells results in degradation of all PeBoW complex components and prevents maturation of 28S rRNA, thereby inhibiting ribosome biogenesis. WDR12 depletion compromises GSC proliferation and inhibits orthotopic tumor growth in vivo. |
shRNA knockdown, rRNA processing assay (28S maturation), western blot for complex component stability, orthotopic xenograft |
Frontiers in oncology |
Medium |
34868955
|
| 2026 |
DR5 competes with p65 for binding to WDR12, a linker protein of the CUL4B-DDB1 E3 ubiquitin ligase complex. By competitively binding WDR12, DR5 reduces ubiquitin-mediated proteasomal degradation of p65, thereby enhancing NF-κB signaling and promoting transcriptional upregulation of DR5 and BCL2 in renal cell carcinoma. |
Co-immunoprecipitation, competitive binding assays, gain- and loss-of-function experiments, ubiquitination assays, in vitro and in vivo models |
Cell death and differentiation |
Medium |
41872532
|
| 2024 |
WDR12 knockdown in colorectal cancer cells downregulates RAC1 expression, which in turn reduces proliferation and promotes apoptosis. mRNA chip-sequencing and IPA after WDR12 knockdown identified activation of cell cycle checkpoint kinase proteins in the checkpoint control signaling pathway. |
shRNA knockdown, mRNA chip-sequencing, IPA pathway analysis, cell proliferation and apoptosis assays (Celigo, MTT, Caspase-3/7), in vivo xenograft |
Molecular and cellular biochemistry |
Low |
38341833
|