Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3390/nano12050771

PubMed

Publishing type：Research paper (scientific journal)   Publisher：{MDPI} {AG}  

DOI： 10.3390/ijms22063110

Scopus

PubMed

Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media {LLC}  

DOI： 10.1038/s41598-021-84750-4

Web of Science

Scopus

PubMed

Publishing type：Research paper (scientific journal)   Publisher：Scientific Reports  

DOI： 10.1038/s41598-020-64604-1

Scopus

PubMed

Publishing type：Research paper (scientific journal)   Publisher：Neuroendocrinology Letters  

Scopus

Publishing type：Research paper (scientific journal)   Publisher：Elsevier {BV}  

DOI： 10.1016/j.neuint.2019.04.003

Web of Science

Scopus

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1371/journal.pone.0207533

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Nature Publishing Group  

Epidermal growth factor receptor (EGFR) signaling and its downregulation upon ligand binding have been extensively documented. However, the mechanisms by which cells maintain steady-state EGFR expression remain poorly understood. Here, we report a novel role of Golgi-localized, γ-adaptin ear-containing, ADP ribosylation factor-binding protein 2 (GGA2) in the control of EGFR turnover. Whereas GGA1-or GGA3-depletion increased EGFR expression, GGA2-depletion by RNAi greatly reduced steady-state expression of EGFR, reflecting enhanced lysosomal degradation of EGFR. Subsequent pull-down assays showed interactions of VHS-GAT domains from three GGAs with the cytoplasmic juxtamembrane region (jxt) of EGFR, which was dependent on N108 in the VHS domain. Proximity ligation assay also revealed the steady-state interaction between GGA2 and EGFR in situ. Moreover, reduced expression of EGFR in GGA2-depleted cells was reversed by additional depletion of GGA1 or GGA3, suggesting that GGA1 and GGA3 promote EGFR degradation. In addition, GGA2-depleted cells had reduced EGF signaling and cell proliferation in cell culture and xenograft experiments. Finally, GGA2 was upregulated in 30.8% of human hepatocellular carcinomas and 23.3% of colorectal cancers. Together, these results indicate that GGA2 supports cell growth by interacting with EGFR for sustaining the receptor expression.

DOI： 10.1038/s41598-018-19542-4

Web of Science

Scopus

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1371/journal.pone.0209441

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.2220/biomedres.39.179

PubMed

Publishing type：Research paper (scientific journal)   Publisher：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

The ubiquitin-proteasome system and autophagy are crucially important for proteostasis in cells. These pathways are interdependent, and dysfunction in either pathway causes accumulation of ubiquitin-positive aggregates, a hallmark of human pathological conditions. To elucidate in vivo compensatory action(s) against proteasomal dysfunction, we developed mice with reduced proteasome activity in their livers. The mutant mice exhibited severe liver damage, accompanied by formation of aggregates positive for ubiquitin and p62/Sqstm1, an adaptor protein for both selective autophagy and the anti-oxidative Keap1-Nrf2 pathway. These aggregates were selectively entrapped by autophagosomes, and pathological features of livers with impaired proteasome activity were exacerbated by simultaneous suppression of autophagy. In contrast, concomitant loss of p62/Sqstm1 had no apparent effect on the liver pathology though p62/Sqstm1 was indispensable for the aggregates formation. Furthermore, defective proteasome function led to transcriptional activation of the Nrf2, which served as a physiological adaptation. Our in vivo data suggest that cells contain networks of cellular defense mechanisms against defective proteostasis.

DOI： 10.1074/jbc.M114.580357

Web of Science

PubMed

Publishing type：Research paper (scientific journal)   Publisher：AMER SOC MICROBIOLOGY  

Recent findings have suggested that the autophagic isolation membrane (IM) might originate from a domain of the endoplasmic reticulum (ER) called the omegasome. However, the morphological relationships between ER, omegasome, and IM remain unclear. In the present study, we found that hybrid structures composed of a double FYVE domain- containing protein 1 (DFCP1)positive omegasome and the IM accumulated in Atg3- deficient mouse embryonic fibroblasts (MEFs). Moreover, correlative light and electron microscopy and immunoelectron microscopy revealed that green fluorescent protein (GFP)- tagged DFCP1 was localized on tubular or vesicular elements adjacent to the IM rims. Through detailed morphological analyses, including optimization of a fixation method and electron tomography, we observed a cluster of thin tubular structures between the IM edges and ER, part of which were continuous with IM and/ or ER. The formation of these thin tubular clusters was observed in several cell lines and MEFs deficient for Atg5, Atg7, or Atg16L1 but not in FIP200- deficient cells, suggesting that they were relevant to the earlier events in autophagosome formation. Taken together, our findings indicate that these tubular profiles represent a part of the omegasome that links the ER with the IM.

DOI： 10.1128/MCB.01327-13

Web of Science

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Presentation type：Poster presentation  

Language：Japanese   Presentation type：Poster presentation  

Language：Japanese   Presentation type：Poster presentation  

Student's Award 優秀賞 受賞

Language：Japanese   Presentation type：Poster presentation  

Language：Japanese   Presentation type：Oral presentation (general)  

Language：Japanese   Presentation type：Poster presentation  

Language：Japanese   Presentation type：Oral presentation (general)  

Language：Japanese   Presentation type：Oral presentation (general)  

Language：Japanese   Presentation type：Poster presentation  

Language：Japanese   Presentation type：Poster presentation  

Language：Japanese   Presentation type：Oral presentation (general)  

Language：Japanese   Presentation type：Oral presentation (general)  

Language：Japanese   Presentation type：Poster presentation  

Language：English   Presentation type：Poster presentation