Abstract 1583: Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development

Author(s):  
Yafang Li ◽  
Xiangjun Xiao ◽  
Ivan Gorlov ◽  
Younghun Han ◽  
Rayjean Hung ◽  
...  
Oncotarget ◽  
2019 ◽  
Vol 10 (19) ◽  
pp. 1760-1774
Author(s):  
Yafang Li ◽  
Xiangjun Xiao ◽  
Yohan Bossé ◽  
Olga Gorlova ◽  
Ivan Gorlov ◽  
...  

2013 ◽  
Vol 12 (8) ◽  
pp. 1087-1096 ◽  
Author(s):  
Moriyuki Kawauchi ◽  
Mika Nishiura ◽  
Kazuhiro Iwashita

ABSTRACT The sirtuins are members of the NAD + -dependent histone deacetylase family that contribute to various cellular functions that affect aging, disease, and cancer development in metazoans. However, the physiological roles of the fungus-specific sirtuin family are still poorly understood. Here, we determined a novel function of the fungus-specific sirtuin HstD/ Aspergillus oryzae Hst4 (AoHst4), which is a homolog of Hst4 in A. oryzae yeast. The deletion of all histone deacetylases in A. oryzae demonstrated that the fungus-specific sirtuin HstD/AoHst4 is required for the coordination of fungal development and secondary metabolite production. We also show that the expression of the laeA gene, which is the most studied fungus-specific coordinator for the regulation of secondary metabolism and fungal development, was induced in a Δ hstD strain. Genetic interaction analysis of hstD / Aohst4 and laeA clearly indicated that HstD/AoHst4 works upstream of LaeA to coordinate secondary metabolism and fungal development. The hstD/Aohst4 and laeA genes are fungus specific but conserved in the vast family of filamentous fungi. Thus, we conclude that the fungus-specific sirtuin HstD/AoHst4 coordinates fungal development and secondary metabolism via the regulation of LaeA in filamentous fungi.


eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Emi Ito ◽  
Kazuo Ebine ◽  
Seung-won Choi ◽  
Sakura Ichinose ◽  
Tomohiro Uemura ◽  
...  

RAB5 is a key regulator of endosomal functions in eukaryotic cells. Plants possess two different RAB5 groups, canonical and plant-unique types, which act via unknown counteracting mechanisms. Here, we identified an effector molecule of the plant-unique RAB5 in Arabidopsis thaliana, ARA6, which we designated PLANT-UNIQUE RAB5 EFFECTOR 2 (PUF2). Preferential colocalization with canonical RAB5 on endosomes and genetic interaction analysis indicated that PUF2 coordinates vacuolar transport with canonical RAB5, although PUF2 was identified as an effector of ARA6. Competitive binding of PUF2 with GTP-bound ARA6 and GDP-bound canonical RAB5, together interacting with the shared activating factor VPS9a, showed that ARA6 negatively regulates canonical RAB5-mediated vacuolar transport by titrating PUF2 and VPS9a. These results suggest a unique and unprecedented function for a RAB effector involving the integration of two RAB groups to orchestrate endosomal trafficking in plant cells.


BioEssays ◽  
2014 ◽  
Vol 36 (7) ◽  
pp. 706-713 ◽  
Author(s):  
Hannes Braberg ◽  
Erica A. Moehle ◽  
Michael Shales ◽  
Christine Guthrie ◽  
Nevan J. Krogan

2018 ◽  
Vol 20 (2) ◽  
pp. 624-637 ◽  
Author(s):  
Mengyun Wu ◽  
Shuangge Ma

2017 ◽  
Vol 31 (2) ◽  
pp. 184-196 ◽  
Author(s):  
Sida Liao ◽  
Teresa Davoli ◽  
Yumei Leng ◽  
Mamie Z. Li ◽  
Qikai Xu ◽  
...  

2021 ◽  
Vol 3 (12) ◽  
Author(s):  
Viola Halder ◽  
Brianna McDonnell ◽  
Rebecca Shapiro

Candida albicans is an opportunistic fungal pathogen found in the oral mucosa, the gut, the vaginal mucosa, and humans' skin. While C. albicans can cause superficial infections, severe invasive infections can occur in immunocompromised individuals. Understanding the survival mechanisms and pathogenesis of C. albicans is critical for novel antifungal drug discovery. Determining the relationships between different genes can create a genetic interaction map, which can identify complementary gene sets, central to C. albicans survival, as potential drug targets in combination therapy. A genetic approach using the CRISPR-Cas9-based genome editing platform will focus on genetic interaction analysis of C. albicans stress response genes. The ultimate goal is to create a stress response gene deletion library to study its pathogen survival role. This library of single and double stress response gene mutants will be screened under diverse growth conditions to assess their relative fitness. Genetic interaction analysis will help map out epistatic interactions between fungal genes involved in growth, survival, and pathogenesis and uncover putative targets for combination antifungal therapy based on negative or synthetic lethal genetic interactions.


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