Deficiency of a potential 3p21.3 tumor suppressor gene UBE1L (UBA7) does not accelerate lung cancer development in K-rasLA2 mice.
Genetic lesions in chromosomal region 3p21.3 marks one of the earliest events in human lung cancer development. It is hypothesized that one or more tumor suppressor genes reside in this region. Identification and characterization of these genes are important for the understanding of lung cancer initiation. UBE1L (UBA7) is a long-suspected 3p21.3 residing tumor suppressor gene. It encodes the key enzyme that activates ISGylation, a novel, ubiquitination-like, post-translational protein modification system that is inducible by interferon. It has been implicated that ISGylation plays a variety of biological roles ranging from viral defense to tumor surveillance. Here we tested the possible function of ISGylation during lung cancer development by using the Ube1l-deficient mice and the K-ras(LA2) lung cancer mice. Protein ISGylation levels were largely unchanged during lung cancer progression. Ube1l deficiency neither altered the lung cancer progression nor affected the overall survival of K-ras(LA2) lung cancer mice. Our study suggests that Ube1l is not a tumor suppressor gene in K-ras(LA2) lung cancer mouse model. However, as described in the discussion, additional studies with other lung cancer mouse models will be necessary to elucidate the potential tumor suppressor function of UBE1L in K-RAS mutation independent human lung cancers.
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA.
Xiaoyan
X
Yin
Xiuli
X
Cong
Ming
M
Yan
Dong-Er
DE
Zhang
D000818:Animals; D016207:Cytokines / Q000032:analysis; D016147:Genes, Tumor Suppressor; D011905:Genes, ras; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008223:Lymphoma / Q000378:metabolism; D051379:Mice; D013950:Thymus Gland / Q000378:metabolism; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics* / Q000502:physiology; D014452:Ubiquitins / Q000032:analysis
D016207:Cytokines; C489550:G1p2 protein, mouse; D014452:Ubiquitins; D044764:Ubiquitin-Activating Enzymes