Small GTPase RBJ mediates nuclear entrapment of MEK1/MEK2 in tumor progression
Authors: Qiuyan Liu
Cheng Qian
Haibo Liu
Minghua Zhu
Taoyong Chen
Jun Guo
Weiping Zhang
Nan Li
Chaofeng Han
Xuetao Cao
Zhou Yu
Jin Hou
Yan Gu
Chen Wang
Long Cui
Weiqiang Zheng
Mingjin Yang
Tao Wan
Xuhui Zhu
Songqing Tang
Journal: Cancer Cell (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: RBJ; small GTPases; tumorigenesis; tumor progression; gastrointestinal cancers
Affiliations: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China; National Key Laboratory of Medical Molecular Biology and Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China., Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China., National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China., Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China., Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China., National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China; National Key Laboratory of Medical Molecular Biology and Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China; Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China. Electronic address: .

Abstract:  Ras-related small GTPases play important roles in cancer. However, the roles of RBJ, a representative of the sixth subfamily of Ras-related small GTPases, in tumorigenesis and tumor progression remain unknown. Here, we report that RBJ is dysregulated in human gastrointestinal cancers and can promote carcinogenesis and tumor progression via nuclear entrapment of mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)1/MEK2 and activation of ERK1/ERK2. Nucleus-localized RBJ interacts with MEK/ERK and prolongs the duration of MEK/ERK activation. Rbj deficiency abrogates nuclear accumulation of MEK1/MEK2, attenuates ERK1/ERK2 activation, and impairs AOM/DSS-induced colonic carcinogenesis. Moreover, Rbj knockdown inhibits growth of established tumors. Our data suggest that RBJ may be an oncogenic Ras-related small GTPase mediating nuclear accumulation of active MEK1/MEK2 in tumor progression. 

Retracted: No

PubPeer comments:
 Figure 6A. The panels representing Mock-3T3 cells and RBJ-3T3 cells appear to show a group of very similar cells, except for the green color which is missing in the left panel. Shown with blue boxes. Could the authors please check? ![file] , 
 #1 Dear Dr. Elisabeth M Bik: Thank you for raising this concern, which we have looked into very carefully and discussed. We regret that two of the images (Figure 6A, panel 1 and 2) was misincorporated during figure assembly when we were preparing for manuscript submission. After checking the original data, we could show the original images for those images presented in Figure 6A (please see below). Specifically, two image files (derived from 1 original image, the RBJ-3T3 group) were misused by accident at the time. Since each quadrant was cropped out from the original graph, we misused the left lower quadrant from RBJ-3T3 group instead of the right lower quadrant of Mock-3T3 group. The yellow circles indicate the correct image and misused image, respectively. We also regret that we didn t catch this error during subsequent revisions and examinations when the manuscript underwent the review and publication processes. ![file] We re preparing a correction request which we ll submit to the journal shortly. We apologize to our readers for any confusion this unintentional error might have caused. Thank you for your attention. , 
 Erratum, March 2021: https: www.cell.com cancer-cell fulltext S1535-6108(21)00112-4  In preparing the figures of our paper, we made two separate errors in Figures 6A and 7A. In Figure 6A, we inadvertently inserted the BODIPY-BFA staining image of the RBJ-3T3 cells to represent the merged immunofluorescent confocal image for Mock-3T3 cells (the first image from the left). The corrected version of Figure 6A now includes the correct image. In the bottom right panel of Figure 7A, we inadvertently inserted an image showing phospho-ERK1 2 staining in the Rbj+ + group to represent the Cyclin D1 staining in the Rbju2212 u2212 group. The corrected version of Figure 7A now includes the correct image. We apologize for these errors and for any inconvenience that they may have caused. ,