RARRES3 (retinoic acid receptor responder (tazarotene induced) 3)

2012-01-01   Tiffany Scharadin  , Richard L Eckert  

Department of Biochemistry, Molecular Biology, University of Maryland, School of Medicine, Baltimore, Maryland 21201, USA

Identity

HGNC
RARRES3
LOCATION
11q12.3
LOCUSID
5920
ALIAS
HRASLS4,HRSL4,PLA1/2-3,PLAAT-4,RARRES3,RIG1,TIG3
FUSION GENES
Show Gene Fusions

DNA/RNA

Atlas Image
Schematic of the TIG3 gene. Thick red boxes indicate exons.

Description

DNA size: 9658 bp with 4 exons.

Transcription

mRNA size: 779 bp, processed: 495 bp.

Proteins

Note

The C-terminus of TIG3 is believed to be a membrane-anchoring domain which is involved in driving membrane localization and is also required for centrosome localization. Removal of this domain from TIG3 causes it to distribute diffusely throughout the cytoplasm and reduces its ability to decrease cell survival (Deucher et al., 2000; Sturniolo et al., 2003; Sturniolo et al., 2005; Jans et al., 2008; Tsai et al., 2009).
Atlas Image
Schematic of the TIG3 protein. The purple indicates the hydrophilic N-terminus (amino acids 1-134) and green indicates the hydrophobic C-terminus (amino acids 134-164). The orange regions represent conserved elements with the H-rev107 family. Highly conserved regions are labeled.

Description

164 amino acids; 18 kDa protein; contains a hydrophilic N-terminus (1-134) and hydrophobic, membrane-anchoring domain (134-164).

Expression

Ubiquitously expressed; expression is reduced in hyperproliferative diseases including cancer.

Localisation

Cell membrane, centrosome (Scharadin et al., 2011).

Function

TIG3 is a type II tumor suppressor gene which regulates cell proliferation and survival (DiSepio et al., 1998). Loss of TIG3 expression leads to hyperproliferative diseases including psoriasis and cancer. Restoration of TIG3 expression to cancer cell lines decreases cell cycle progression and induces apoptosis causing an overall decrease in viable cells (DiSepio et al., 1998; Huang et al., 2002; Higuchi et al., 2003; Tsai et al., 2009; Scharadin et al., 2011). Localization of TIG3 to the centrosome is believed to be responsible for this decrease in cell survival, which leads to an increase in p21 level, a G1/S phase block, an activation of the caspase cascade, and a reorganization of the microtubule network (Scharadin et al., 2011).
In contrast, expression of TIG3 in normal keratinocytes induces a process of terminal differentiation through the binding to and activation of type I transglutaminase and increase in cornified envelope formation to decrease cell survival (Sturniolo et al., 2003; Sturniolo et al., 2005; Jans et al., 2008). Localization of TIG3 to the cell membrane in keratinocytes is necessary for it to bind type I transglutaminase.

Homology

TIG3 shares homology with the H-rev107 family of class II tumor suppressors and the NlpC/P60 superfamily (Hajnal et al., 1994; DiSepio et al., 1998; Husmann et al., 1998; Anantharaman and Aravind, 2003; Jahng et al., 2003).

Mutations

Note

No known mutations.

Implicated in

Entity name
Various cancers
Note
TIG3 expression is reduced in several cancer including breast, skin, lymphoma, leukemia, kidney, ureter, colorectal, liver, biliary tract, ovary, and uterine.
Disease
Cancer is a disease characterized by uncontrolled cell proliferation.
Prognosis
Cancer prognosis is dependent upon several tumor-specific conditions, including location, size, and metastasis.
Oncogenesis
Loss of TIG3 mRNA and protein expression is observed in several cancers and may be necessary for oncogenesis (DiSepio et al., 1998; Casanova et al., 2001; Duvic et al., 2003; Shyu et al., 2003; Jiang et al., 2005; Lotz et al., 2005; Shyu et al., 2005). Tazarotene treatment of skin cancers leads to increased TIG3 expression and reduced proliferation (Duvic et al., 2000; Duvic et al., 2003). The loss of TIG3 is associated with increased cell proliferation and TIG3 loss may be necessary for cancer progression.
Entity name
Hyperproliferative diseases
Note
Loss of TIG3 expression is associated with hyperproliferative diseases including psoriasis and cancer.
TIG3 mRNA and protein levels are reduced in psoriatic lesions. Treatment with tazarotene leads to an increase in TIG3 levels and restoration of the normal epidermal condition (Duvic et al., 2000). Hypermethylation of the TIG3 promoter is a possible mechanism for reduced expression in psoriasis (Kwong et al., 2005).
Disease
Psoriasis is a common disorder of the skin which is characterized by inflammation and hyperproliferation of the epidermis.
Prognosis
Psoriasis is a non-fatal, chronic disorder that can be controlled with treatment.

Breakpoints

Note

No breakpoints known.

Article Bibliography

Pubmed IDLast YearTitleAuthors
126201212003Evolutionary history, structural features and biochemical diversity of the NlpC/P60 superfamily of enzymes.Anantharaman V et al
120942682002The class II tumour suppressor gene RARRES3 maps to 11q12, not 11q23.Auer RL et al
115872092001The class II tumor-suppressor gene RARRES3 is expressed in B cell lymphocytic leukemias and down-regulated with disease progression.Casanova B et al
110788052000The carboxy-terminal hydrophobic domain of TIG3, a class II tumor suppressor protein, is required for appropriate cellular localization and optimal biological activity.Deucher A et al
98439711998Identification and characterization of a retinoid-induced class II tumor suppressor/growth regulatory gene.DiSepio D et al
109558112000Expression of a retinoid-inducible tumor suppressor, Tazarotene-inducible gene-3, is decreased in psoriasis and skin cancer.Duvic M et al
146322112003Tazarotene-induced gene 3 is suppressed in basal cell carcinomas and reversed in vivo by tazarotene application.Duvic M et al
82902591994Subtraction cloning of H-rev107, a gene specifically expressed in H-ras resistant fibroblasts.Hajnal A et al
128790062003Induction of TIG3, a putative class II tumor suppressor gene, by retinoic acid in head and neck and lung carcinoma cells and its association with suppression of the transformed phenotype.Higuchi E et al
120146532002The retinoid-inducible gene I: effect on apoptosis and mitogen-activated kinase signal pathways.Huang SL et al
97719741998Transcriptional and translational downregulation of H-REV107, a class II tumour suppressor gene located on human chromosome 11q11-12.Husmann K et al
145965942003Lecithin retinol acyltransferase is a founder member of a novel family of enzymes.Jahng WJ et al
177628582008Localization of the TIG3 transglutaminase interaction domain and demonstration that the amino-terminal region is required for TIG3 function as a keratinocyte differentiation regulator.Jans R et al
157423942005Decreased expression of type II tumor suppressor gene RARRES3 in tissues of hepatocellular carcinoma and cholangiocarcinoma.Jiang SY et al
154553912005Silencing of the retinoid response gene TIG1 by promoter hypermethylation in nasopharyngeal carcinoma.Kwong J et al
158564682005Suppression of the TIG3 tumor suppressor gene in human ovarian carcinomas is mediated via mitogen-activated kinase-dependent and -independent mechanisms.Lotz K et al
218580382011TIG3 tumor suppressor-dependent organelle redistribution and apoptosis in skin cancer cells.Scharadin TM et al
160804752005Expression and regulation of retinoid-inducible gene 1 (RIG1) in breast cancer.Shyu RY et al
128383162003RARRES3 expression positively correlated to tumour differentiation in tissues of colorectal adenocarcinoma.Shyu RY et al
158463042005A novel transglutaminase activator forms a complex with type 1 transglutaminase.Sturniolo MT et al
192456942009Induction of apoptosis by the retinoid inducible growth regulator RIG1 depends on the NC motif in HtTA cervical cancer cells.Tsai FM et al

Citation

Tiffany Scharadin ; Richard L Eckert

RARRES3 (retinoic acid receptor responder (tazarotene induced) 3)

Atlas Genet Cytogenet Oncol Haematol. 2012-01-01

Online version: http://atlasgeneticsoncology.org/gene/42051/rarres3-(retinoic-acid-receptor-responder-(tazarotene-induced)-3)