TIG3 Tumor Suppressor-Dependent Organelle Redistribution and Apoptosis in Skin Cancer Cells

Scharadin, Tiffany M.; Jiang, Haibing; Jans, Ralph; Rorke, Ellen A.; Eckert, Richard L.

doi:10.1371/journal.pone.0023230

Cited by 17 publications

(39 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We previously reported that TIG3 reduces cell survival (Jans et al, 2008;Scharadin et al, 2011;Sturniolo et al, 2003); however, little is known about the mechanism of growth suppression. In the present study, we demonstrate that TIG3 localizes to the centrosome, as shown by colocalization with the centriole and centrosome markers, c-tubulin and pericentrin.…”

Section: Discussionmentioning

confidence: 99%

TIG3 Interaction at the Centrosome Alters Microtubule Distribution and Centrosome Function

Scharadin

Jiang

Martin

et al. 2012

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

SummaryTIG3 is an important pro-differentiation regulator that is expressed in the suprabasal epidermis. We have shown that TIG3 activates selective keratinocyte differentiation-associated processes leading to cornified envelope formation. However, TIG3 also suppresses cell proliferation by an unknown mechanism. Our present studies suggest that cessation of growth is mediated through the impact of TIG3 on the centrosome and microtubules. The centrosome regulates microtubule function in interphase cells and microtubule spindle formation in mitotic cells. We show that TIG3 colocalizes with c-tubulin and pericentrin at the centrosome. Localization of TIG3 at the centrosome alters microtubule nucleation and reduces anterograde microtubule growth, increases acetylation and detyrosination of a-tubulin, increases insoluble tubulin and drives the formation of a peripheral microtubule ring adjacent to the plasma membrane. In addition, TIG3 suppresses centrosome separation, but not duplication, and reduces cell proliferation. We propose that TIG3 regulates the formation of the peripheral microtubule ring observed in keratinocytes of differentiated epidermis and also has a role in the cessation of proliferation in these cells.

show abstract

Section: Discussionmentioning

confidence: 99%

TIG3 Interaction at the Centrosome Alters Microtubule Distribution and Centrosome Function

Scharadin

Jiang

Martin

et al. 2012

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

show abstract

“…TIG3 localizes to the plasma membrane and at the centrosome in normal keratinocytes and skin cancer cells (Sturniolo et al , 2005; Sturniolo et al , 2003; Scharadin et al , 2011; Scharadin et al , 2012). The C-terminal hydrophobic region serves to anchor TIG3 to the cell membrane (Deucher et al , 2000; Sturniolo et al , 2005; Sturniolo et al , 2003) where it activates transglutaminase.…”

Section: Introductionmentioning

confidence: 99%

Pericentrosomal Localization of the TIG3 Tumor Suppressor Requires an N-Terminal Hydrophilic Region Motif

Scharadin

Adhikary

Shaw

et al. 2014

Journal of Investigative Dermatology

Self Cite

View full text Add to dashboard Cite

TIG3 is a tumor suppressor protein that plays a key role in controlling cell proliferation. TIG3 is observed at reduced levels in epidermal squamous cell carcinoma, and restoration of expression in skin cancer cells reduces cell survival. TIG3 suppresses cell survival via mechanisms that involve localization at the plasma membrane and at the centrosome. TIG3 interacts at the plasma membrane to activate enzymes involved in keratinocyte terminal differentiation, and at the centrosome to inhibit daughter centrosome separation during mitosis leading to cessation of cell proliferation and induction of apoptosis. An important goal is identifying the motifs required for TIG3 localization at these intracellular sites as a method to understand the function of TIG3 at each location. TIG3 encodes an N-terminal hydrophilic region (amino acids 1–135) and a C-terminal membrane anchoring domain (amino acids 135–164). We show that the C-terminal hydrophobic domain targets intact TIG3 to the plasma membrane, but when isolated as an independent element localizes at the mitochondria. We further demonstrate that a segment of the N-terminal hydrophilic region targets the centrosome. These studies provide important insights regarding the mechanisms that guide subcellular localization of this keratinocyte survival regulator.

show abstract

“…Both genes are expressed in normal tissues in a tissue-specific manner and are downregulated in various cancer tissues [15-18]. These proteins exhibit growth-suppressive activities when ectopically expressed in various types of cancer cells and RAS-transformed fibroblasts [6,8,11,13,19-22]. In addition, terminal differentiation of keratinocytes has been observed in cells with induced RIG1 expression [13,23].…”

Section: Introductionmentioning

confidence: 99%

H-rev107 regulates prostaglandin D2 synthase-mediated suppression of cellular invasion in testicular cancer cells

Shyu

Wang

et al. 2013

J Biomed Sci

View full text Add to dashboard Cite

BackgroundH-rev107 is a member of the HREV107 type II tumor suppressor gene family which includes H-REV107, RIG1, and HRASLS. H-REV107 has been shown to express at high levels in differentiated tissues of post-meiotic testicular germ cells. Prostaglandin D2 (PGD2) is conjectured to induce SRY-related high-mobility group box 9 (SOX9) expression and subsequent Sertoli cell differentiation. To date, the function of H-rev107 in differentiated testicular cells has not been well defined.ResultsIn the study, we found that H-rev107 was co-localized with prostaglandin D2 synthase (PTGDS) and enhanced the activity of PTGDS, resulting in increase of PGD2 production in testis cells. Furthermore, when H-rev107 was expressed in human NT2/D1 testicular cancer cells, cell migration and invasion were inhibited. Also, silencing of PTGDS would reduce H-rev107-mediated increase in PGD2, cAMP, and SOX9. Silencing of PTGDS or SOX9 also alleviated H-rev107-mediated suppression of cell migration and invasion.ConclusionsThese results revealed that H-rev107, through PTGDS, suppressed cell migration and invasion. Our data suggest that the PGD2-cAMP-SOX9 signal pathway might play an important role in H-rev107-mediated cancer cell invasion in testes.

show abstract

TIG3 Tumor Suppressor-Dependent Organelle Redistribution and Apoptosis in Skin Cancer Cells

Cited by 17 publications

References 50 publications

TIG3 Interaction at the Centrosome Alters Microtubule Distribution and Centrosome Function

TIG3 Interaction at the Centrosome Alters Microtubule Distribution and Centrosome Function

Pericentrosomal Localization of the TIG3 Tumor Suppressor Requires an N-Terminal Hydrophilic Region Motif

H-rev107 regulates prostaglandin D2 synthase-mediated suppression of cellular invasion in testicular cancer cells

Contact Info

Product

Resources

About