The inducible E3 ubiquitin ligases SIAH1 and SIAH2 perform critical roles in breast and prostate cancers

Knauer, Shirley K.; Mahendrarajah, Nisintha; Roos, Wynand P.; Krämer, Oliver H.

doi:10.1016/j.cytogfr.2015.04.002

Cited by 26 publications

(25 citation statements)

References 94 publications

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“…An increasing body of evidence suggests SIAH1 and SIAH2 play critical functional roles in tumorigenesis, metastasis, and chemo-/radio-sensitivity in cancer treatment [2,[11][12][13]67,68]. Many studies found the expression level of SIAH1 is down-regulated in cancers [63,69,70] and demonstrated a tumour suppression and reversion capacity of SIAH1 [71].…”

Section: Targeting Siahs In Tumorigenesismentioning

confidence: 99%

The substrate binding domains of human SIAH E3 ubiquitin ligases are now crystal clear

Zhang

Wang

Hou

et al. 2017

Biochimica et Biophysica Acta (BBA) - General Subjects

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Section: Targeting Siahs In Tumorigenesismentioning

confidence: 99%

The substrate binding domains of human SIAH E3 ubiquitin ligases are now crystal clear

Zhang

Wang

Hou

et al. 2017

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…The Siah1 protein belongs to the highly conserved family of E3 ubiquitin ligases. Structurally, the Siah1 protein contains two zinc finger cytokine-rich domains and shares 77% identity with Siah-2 [14], but they have different substrate targets [13]. A large number of studies have shown that Siah1 plays a role as a tumor suppressor gene in the process of tumorigenesis and evolution.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that Siah1 is a target of MiRNAs [9][10][11] and other proteins [12] that are likely to affect the occurrence and progress of tumor [13]. Recent studies [14][15][16][17][18] have found that Siah1 plays an important role in promoting apoptosis under hypoxic conditions or by the P53-induced pathway, and during the process of tumor development, Siah1 behaves as a tumor suppressor.…”

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confidence: 99%

Downregulation of Siah1 promotes colorectal cancer cell proliferation and migration by regulating AKT and YAP ubiquitylation and proteasome degradation

et al. 2020

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Background: Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Siah E3 ubiquitin protein ligase 1 (Siah1) has been identified as a tumor suppressor gene and plays an important role in the development of malignant tumors. However, the potential role and molecular mechanism of Siah1 in the development and progression of CRC is still unclear. Methods: To explore the role and molecular mechanism of Siah1 in the development and progression of CRC, we examined the expression of Siah1 in CRC tissue samples and analyzed its association with progression and prognosis in CRC. In addition, overexpression and knockdown of Siah1 was used to investigate its activity in CRC cells. We also use bioinformatics to analyze and verify the significant roles of Siah1 in critical signaling pathways of CRC. Results: We found that the expression of Siah1 was significantly downregulated in CRC tissues, and low expression of Siah1 was associated with aggressive TNM staging and poor survival of CRC patients. Moreover, we revealed that overexpression of Siah1 in CRC cells markedly inhibited CRC cell proliferation and invasion in vitro and in vivo, while knockdown of Siah1 enhanced CRC cell proliferation and invasion. Furthermore, we found that Siah1 prohibited cell proliferation and invasion in CRC partially through promoting AKT (the serine-threonine protein kinase) and YAP (yes associated protein) ubiquitylation and proteasome degradation to regulate the activity of MAPK(mitogen-activated protein kinase 1), PI3K-AKT (phosphatidylinositol 3-kinase-the serine-threonine protein kinase) and Hippo signaling pathways. Conclusions: These findings suggested that Siah1 is a novel potential prognostic biomarker and plays a tumor suppressor role in the development and progression of CRC.

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“…The ubiquitin ligase complex of SIAH1 gene contains SIAH1 interacting protein, F-box protein Ebi and Skp1 gene. Interestingly, SIAH2, an isoform of SIAH gene plays an important role in diverse signaling pathways and having high sequence similarity with SIAH1 but possess contrary roles in cancer, since SIAH1 more often acting as a tumor suppressor whereas, SIAH2 acts as a proto-oncogene [130].…”

Section: Siah1mentioning

confidence: 99%

Molecular Chaperones and Ubiquitin Proteasome System in Tumor Biogenesis: An Overview

Ambasta¹

2016

CBCM

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The hallmark feature in cancer is uncontrolled cell-division and altered protein expression. Currently, cancer is one of the most detrimental diseases encountered by a large population across the globe. However, an absolute treatment strategy has still not been achieved by the researchers. Further, molecular mechanism and therapeutic to combat this lethal disease is a baffling issue. Molecular chaperones and ubiquitin proteasome system is mainly responsible for the maintenance of protein homeostasis and thus playing a crucial role in the cancer pathophysiology. Molecular chaperones are a superfamily of proteins which expressions are triggered under physiological, pharmacological and environmental insults and playing a protective role for cell survival. However, beyond a threshold of protection, molecular chaperones are unable to provide proper shape of non functional proteins that accumulate unwanted protein the cellular milieu. In order to get rid off these accumulated proteins ubiquitin proteasome system comes into action where an E3 ligase, specific enzymes of ubiquitination system, play a decisive role in the turnover of many essential regulatory proteins involved in cancer. It also mediates numerous functions, for instance, cell death, cell growth and DNA repair. Since, both molecular chaperones and E3 ligases have been involved in the progression of cancers it is necessary to understand and implement the role of these two molecules to use as diagnostic markers to treat cancer. Herein, we have comprehensively discussed the functional role of molecular chaperones, their differential protein expressions and a possible correction mechanism in cancer. Furthermore, comprehensive information has been documented regarding E3 ligases and their associated role in cancer that may be used as potential diagnostic biomarker for the treatment of various cancers.

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The inducible E3 ubiquitin ligases SIAH1 and SIAH2 perform critical roles in breast and prostate cancers

Cited by 26 publications

References 94 publications

The substrate binding domains of human SIAH E3 ubiquitin ligases are now crystal clear

The substrate binding domains of human SIAH E3 ubiquitin ligases are now crystal clear

Downregulation of Siah1 promotes colorectal cancer cell proliferation and migration by regulating AKT and YAP ubiquitylation and proteasome degradation

Molecular Chaperones and Ubiquitin Proteasome System in Tumor Biogenesis: An Overview

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