PUBLICATION

UBTOR/KIAA1024 regulates neurite outgrowth and neoplasia through mTOR signaling

Authors

Zhang, H., Zhang, Q., Gao, G., Wang, X., Wang, T., Kong, Z., Wang, G., Zhang, C., Wang, Y., Peng, G.

ID

ZDB-PUB-180807-8

Date

2018

Source

PLoS Genetics 14: e1007583 (Journal)

Registered Authors

Peng, Gang, Zhang, Cuizhen, Zhang, Hefei

Keywords

none

MeSH Terms

Rats
Animals
Humans
PC12 Cells
RNA, Small Interfering/genetics
RNA, Small Interfering/metabolism
Neuronal Outgrowth/genetics*
Receptors, Cell Surface/genetics
Receptors, Cell Surface/metabolism*
Zebrafish/genetics
Zebrafish/metabolism
Mice, Inbred BALB C
Mice
Cell Line, Tumor
Cell Proliferation/genetics*
Signal Transduction
Gene Expression Regulation*
Female
Chromosome Mapping
TOR Serine-Threonine Kinases/genetics
TOR Serine-Threonine Kinases/metabolism*
HEK293 Cells
Xenograft Model Antitumor Assays
Gene Deletion
Mice, Nude
Rats, Sprague-Dawley

(all 26)

PubMed

30080879 Full text @ PLoS Genet.

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.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
EGFP	nkuasgfp1aTg; zf3111Et	standard conditions	Day 5	brain	IFL	Fig. S1
EGFP	nkuasgfp1aTg; zf3111Et	standard conditions	Protruding-mouth	habenula	IFL	Fig. S1
EGFP	nkuasgfp1aTg; zf3111Et	standard conditions	Day 5	spinal cord	IFL	Fig. S1
minar1	AB	standard conditions	Protruding-mouth	habenula	ISH	Fig. S1
minar1	AB	standard conditions	Day 5	habenula	ISH	Fig. S1

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
minar1^{zf3113/zf3113} (AB)	control	Day 5	behavior process quality, abnormal	Fig. S7
minar1^{zf3113/zf3113} (AB)	control	Days 45-89	behavior process quality, abnormal	Fig. S7
minar1^{zf3113/zf3113} (AB)	control	Days 45-89	fear response process quality, abnormal	Fig. S7
minar1^{zf3113/zf3113} (AB)	standard conditions	Day 5	head ab6-rps6k labeling increased amount, abnormal	Fig. 7
minar1^{zf3113/zf3113} (AB)	standard conditions	Day 5	TOR signaling increased occurrence, abnormal	Fig. 7
minar1^{zf3113/zf3113} (AB)	fasting	Days 14-20	brain ab6-rps6k labeling increased amount, abnormal	Fig. 7
minar1^{zf3113/zf3113} (AB)	fasting	Days 14-20	brain ab8-rps6 labeling increased amount, abnormal	Fig. 7
minar1^{zf3113/zf3113} (AB)	fasting	Days 14-20	TOR signaling increased occurrence, abnormal	Fig. 7
minar1^{zf3113/zf3113} (AB)	food availability, fasting	Days 14-20	brain ab8-rps6 labeling increased amount, abnormal	Fig. 7
minar1^{zf3113/zf3113} (AB)	food availability, fasting	Days 14-20	TOR signaling increased occurrence, abnormal	Fig. 7

1 - 10 of 10

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
nkuasgfp1aTg	Tg(5xUAS:EGFP)	Transgenic Insertion
zf3111Et	Et(Gal4ff)	Transgenic Insertion
zf3112		Small Deletion	minar1
zf3113		Small Deletion	minar1

1 - 4 of 4

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
minar1	CRISPR1-minar1	CRISPR
minar1	TALEN1-minar1	TALEN

Fish

Fish
AB
minar1^{zf3113/zf3113} (AB)
nkuasgfp1aTg; zf3111Et

Antibodies

Name	Type	Isotypes	Host Organism
Ab6-rps6k	monoclonal	IgG	Rabbit
Ab7-rps6k	monoclonal		Rabbit
Ab8-rps6	monoclonal	IgG	Rabbit

Orthology

Gene	Orthology
minar1

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
GAL4FF	EFG	GAL4FF

Mapping

Zhang et al., 2018 ZDB-PUB-180807-8 PMID:30080879

UBTOR/KIAA1024 regulates neurite outgrowth and neoplasia through mTOR signaling

Zhang et al., 2018

ZDB-PUB-180807-8
PMID:30080879