You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.

Title: UBTOR/KIAA1024 regulates neurite outgrowth and neoplasia through mTOR signaling}
Article:
Abstract:
The mTOR signaling pathways regulate cell growth and are involved in multiple human diseases. Here, we identify UBTOR, a previously unannotated gene as a functional player in regulating cell growth and mTOR signaling. Reduction of UBTOR function in cultured hippocampal neurons and PC12 cells promotes neurite outgrowth. UBTOR depletion activates mTOR signaling and promotes cell growth, whilst UBTOR overexpression suppresses colony formation in cancer cell lines. Studies in cultured cells and zebrafish model show that UBTOR inhibits mTOR signaling by stabilizing the mTOR complex component DEPTOR, and ubtor gene disruption result in higher mTOR activity and aggravate HRAS( G12V) induced neoplasia in the zebrafish. Lastly, UBTOR depletion promotes tumor growth and mTOR signaling in a xenograft mouse model. Together, our results demonstrate how UBTOR regulates cell growth and neoplasia via mTOR signaling.
Introduction:
Mechanistic target of rapamycin( mTOR) signaling is a central pathway that controls cell metabolism, growth, proliferation and survival. Clinically the mTOR pathway is implicated in human diseases including tumor formation, obesity, epilepsy, autism and neurodegeneration[1–3]. mTOR signaling activity is regulated by various factors at multiple cellular organelles[4]. The central catalytic protein mTOR forms two complexes mTORC1 and mTORC2 through interactions with a number of proteins. These mTOR interacting proteins exert important regulatory roles on mTOR activity. A protein of interest is DEPTOR, a component of both mTOR complexes and an inhibitor of mTOR signaling found only in the vertebrate species[5]. DEPTOR is phosphorylated and ubiquitylated when mTORC1 signaling pathway is activated by serum stimulation, which subsequently results in its degradation[6–8]. Here, we identify Ubtor as a functional player in regulating cell growth and mTOR signaling. Ubtor is a vertebrate-specific, previously unannotated gene except being listed as a downregulated or mutated gene in tumor tissues[9–11]. Ubtor encodes a protein without any known functional domains. We first show reductions of Ubtor expression levels in cultured hippocampal neurons and PC12 cells promote neurite outgrowth. In addition, UBTOR depletion promotes cell growth in HEK293T and U87MG cells, whilst UBTOR overexpression suppresses colony formation in HEK293T and T24 cells. We next show reduction of Ubtor promotes mTOR signaling. Mechanistic studies in cultured cells show UBTOR interacts with DEPTOR and mTOR complexes. Further studies show UBTOR stabilizes DEPTOR and regulates DEPTOR’s ubiquitination. Lastly, ubtor gene disruption in zebrafish increases mTOR activity and aggravates HRAS( G12V) induced neoplasia in the intact animals. In parallel, Ubtor depletion promotes tumor growth and mTOR signaling in xenograft-bearing mice. Together, our results demonstrate how Ubtor regulates cell growth and neoplasia via mTOR signaling.
Discussion:
In this study, UBTOR depletion promotes neurite and cellular growth, whilst UBTOR overexpression suppresses colony formation in cancer cell lines. Mechanistic studies in cultured cells revealed UBTOR stabilized DEPTOR, a component of the mTOR complexes, to inhibit the mTOR signaling. Investigations in the zebrafish model further showed disruption of ubtor gene upregulated the mTOR signaling and promoted HRAS( G12V) mediated tumor formation in intact animals. Similarly, UBTOR depletion promoted tumor growth and mTOR signaling in a xenograft mouse model. These findings demonstrate how Ubtor regulates cellular growth and neoplasia via mTOR signaling. Ubtor is an unannotated gene and present in the vertebrate species only. It encodes a protein without any known functional domains despite of exhaustive sequence homology-based searches[23–25]. Ubtor protein is highly conserved in the vertebrates, with the shark protein shares 55% identities with the human protein. Searches of protein prediction servers[26–27] and protein-protein interaction databases[28] provided no clues into the function of Ubtor protein. No previous studies have indicated the function of the Ubtor gene or protein product, except that UBTOR gene was listed as one of the top down-regulated genes in adrenocortical adenoma[10], and a top-ranked mutated gene in pancreatic cancer[9, 11]. Expression analyses of human tumor samples also indicated UBTOR was markedly downregulated in adrenocortical cancer, pheochromocytoma and paraganglioma, and glioma. The present study highlights Ubtor’s functions in the cellular growth and the mTOR signaling. Abnormal activation of the mTOR signaling may provide explanation why UBTOR is downregulated or mutated in tumor tissues. Consistent with this view, our results show UBTOR knock-down promote growth in HEK293T and U87MG cells, and overexpression of UBTOR reduced colony formation in both the HEK293T cells and the carcinoma T24 cells. Enhancement of HRASG12V mediated tumor formation in the homozygous ubtor zebrafish mutant and larger xenograft tumor growth of UBOTR-depleted U87MG cells in the nude mice further support involvement of Ubtor in neoplasia. Interestingly, we show that NGF treatment in PC12 cells upregulate Ubtor expression. The induction of higher Ubtor expressions levels upon mTOR signaling activation may keep the mTOR signaling activity in check. Thus, Ubtor constitutes a novel negative feedback mechanism[29–31] to control mTOR signaling. mTOR signaling activity is tightly regulated by various interacting proteins of the catalytic mTOR protein. DEPTOR is an integral component of both mTOC complexes and it functions an inhibitor of the mTOR signaling. Previous studies show that DEPTOR is ubiquitylated when mTOR signaling pathway is activated, which results in its degradation[6–8]. Our results show that UBTOR reduces ubiquitination of DEPTOR and stabilizes DEPTOR expression levels. Because the N terminal UBTOR1-467 binds to DEPTOR, a parsimonious model may indicate UBTOR is a deubiquitinating enzyme( DUB). Standard sequence-based homology searches fail to reveal an existence of DUB domain or any other functional domains in the UBTOR protein[23], neither do other specialized methods meant to detect remote homologies[24, 25]. However, the primary sequences of DUB are diverse[32, 33]. Future studies will be required to determine if DUBTOR harbors deubiquitinating activity, or other mechanisms such as interference with the DEPTOR E3 ligase SCF[34] or trapping of mTOR complexes on the endoplasmic reticulum are involved. In summary, our study provides insights into how Ubtor regulate cellular growth and mTOR signaling. Manipulations of Ubtor function may potentially be utilized to optimize mTOR signaling activities for treatments of cancers and other diseases.
Cell growth is a fundamental aspect of cell behavior in all organisms . The mTOR signaling pathways are essential for cell growth and clinically mis-regulation of the mTOR pathways are implicated in human diseases including tumor formation , obesity , epilepsy , autism and neurodegeneration . Here , we identify a novel gene , Ubtor as a functional player in regulating cell growth and mTOR signaling . Inhibiting Ubtor function promotes cell growth in neurons and cancer cells . Increasing Ubtor function reduces cancer cell growth . Functional analyses in human cells and the zebrafish model indicate Ubtor inhibits mTOR signaling by stabilizing the mTOR complex component DEPTOR , and ubtor gene disruption resulted in higher mTOR activity and aggravated cancer formation in the zebrafish . UBTOR depletion promotes tumor growth and mTOR signaling in xenograft-bearing mice . Thus our study provide evidence that Ubtor constitutes a novel negative feedback mechanism to control mTOR signaling and cell growth , and manipulations of Ubtor function may potentially be utilized to optimize mTOR signaling activities for treatments of cancers and other diseases .