TARBP2 Suppresses Ubiquitin-Proteasomal Degradation of HIF-1α in Breast Cancer

Li, Jie-Ning; Chen, Pai‐Sheng; Chiu, Ching-Feng; Lyu, Yu-Jhen; Lo, Chiao; Tsai, Li-Wei; Wang, Mingyang

doi:10.3390/ijms23010208

Cited by 7 publications

(3 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Under the circumstance of hypoxia, HIF-1α is negatively regulated by FBXW7-mediated ubiquitination and proteolysis in human ovarian cancer cells, proposing an underlying direction for energy reprogramming and angiogenesis ( 91 ). The oncoprotein TAR (HIV-1) RNA binding protein 2 (TARBP2) can elevate the stability of HIF-1α by decreasing its ubiquitination level through decreasing the E3 ligases activity including FBXW7 in BC cells ( 125 ).…”

Section: Fbxw7 and The Hallmarks Of Cancermentioning

confidence: 99%

FBXW7 and the Hallmarks of Cancer: Underlying Mechanisms and Prospective Strategies

et al. 2022

View full text Add to dashboard Cite

FBXW7, a member of the F-box protein family within the ubiquitin–proteasome system, performs an indispensable role in orchestrating cellular processes through ubiquitination and degradation of its substrates, such as c-MYC, mTOR, MCL-1, Notch, and cyclin E. Mainly functioning as a tumor suppressor, inactivation of FBXW7 induces the aberrations of its downstream pathway, resulting in the occurrence of diseases especially tumorigenesis. Here, we decipher the relationship between FBXW7 and the hallmarks of cancer and discuss the underlying mechanisms. Considering the interplay of cancer hallmarks, we propose several prospective strategies for circumventing the deficits of therapeutic resistance and complete cure of cancer patients.

show abstract

Section: Fbxw7 and The Hallmarks Of Cancermentioning

confidence: 99%

FBXW7 and the Hallmarks of Cancer: Underlying Mechanisms and Prospective Strategies

et al. 2022

View full text Add to dashboard Cite

show abstract

“…HIF-1α is regulated by pro-inflammatory cytokines (IL-1b, and TNF-α,) in an NF-kB-dependent manner. The level of protein is controlled for example by TARBP2, which prevents its proteasomal ubiquitination to enhance HIF-1α protein stability [ 117 ]. A significant correlation of these proteins is observed with breast cancer pathogenesis, and progression process, and is linked to hypoxia.…”

Section: Micrornas (Mirnas) In Breast Cancermentioning

confidence: 99%

Obesity as a Risk Factor for Breast Cancer—The Role of miRNA

Hanusek

Karczmarski

Litwiniuk

et al. 2022

IJMS

View full text Add to dashboard Cite

Breast cancer (BC) is the most common cancer diagnosed among women in the world, with an ever-increasing incidence rate. Due to the dynamic increase in the occurrence of risk factors, including obesity and related metabolic disorders, the search for new regulatory mechanisms is necessary. This will help a complete understanding of the pathogenesis of breast cancer. The review presents the mechanisms of obesity as a factor that increases the risk of developing breast cancer and that even initiates the cancer process in the female population. The mechanisms presented in the paper relate to the inflammatory process resulting from current or progressive obesity leading to cell metabolism disorders and disturbed hormonal metabolism. All these processes are widely regulated by the action of microRNAs (miRNAs), which may constitute potential biomarkers influencing the pathogenesis of breast cancer and may be a promising target of anti-cancer therapies.

show abstract

“…In breast cancer, Parkin and TNF receptor-associated factor 6 have been shown to target the ubiquitination of HIF-1α. In addition, GSK-3β can mediate the degradation of HIF-1α in hepatoma cells through FBXW7 ( 20 - 22 ). These studies suggested that FBPs may have a role in HIF-1α regulation.…”

Section: Introductionmentioning

confidence: 99%

FBXO30 functions as a tumor suppressor and an E3 ubiquitin ligase for hZIP1‑mediated HIF‑1α degradation in renal cell carcinoma

Yuan

Liu

et al. 2023

Int J Oncol

View full text Add to dashboard Cite

Studies on clear cell renal cell carcinoma (ccRCC) are gaining momentum due to its high malignancy and potential to metastasize. F-box protein 30 (FBXO30) is a member of the F-box protein family; however, its role and mechanism in cancer remains to be fully elucidated. Western blotting, reverse transcription-quantitative PCR and immunohistochemsitry were performed to detect the expression levels of FBXO30 in ccRCC tissues and adjacent normal tissues. Tumor biological function assays and animal experiments were conducted to clarify the inhibitory effect of FBXO30 on the progression and metastasis of ccRCC. Protein half-life assay, MG132 inhibition assay, immunofluorescence assay and co-immunoprecipitation assay were performed to explore the ubiquitination mechanism of FBXO30 and HIF-1α. Zinc supplementation assay was used to verify the regulatory relationship between human ZRT, IRT-like protein 1 (hZIP1), FBXO30 and HIF-1α. The present study revealed that the expression levels of FBXO30 were lower in ccRCC tissues compared with those in normal adjacent tissues. In addition, FBXO30 inhibited the tumorigenesis and metastatic capacity of ccRCC cells in vivo and in vitro . FBXO30 mediated the ubiquitination and degradation of hypoxia-inducible factor-1α (HIF-1α) in ccRCC cells under normoxia, thereby inhibiting the oncogenic effect of HIF-1α. Notably, hZIP1 served as an upstream regulator of FBXO30, regulating the expression of FBXO30 and HIF-1α by recruiting Zn 2+ . In conclusion, the present data suggested that FBXO30 is a novel E3 ubiquitination ligase that can function as a tumor suppressor in ccRCC, and the hZIP1/Zn 2+ /FBXO30/HIF-1α axis may provide potential biomarkers or therapeutic targets for ccRCC.

show abstract

TARBP2 Suppresses Ubiquitin-Proteasomal Degradation of HIF-1α in Breast Cancer

Cited by 7 publications

References 26 publications

FBXW7 and the Hallmarks of Cancer: Underlying Mechanisms and Prospective Strategies

FBXW7 and the Hallmarks of Cancer: Underlying Mechanisms and Prospective Strategies

Obesity as a Risk Factor for Breast Cancer—The Role of miRNA

FBXO30 functions as a tumor suppressor and an E3 ubiquitin ligase for hZIP1‑mediated HIF‑1α degradation in renal cell carcinoma

Contact Info

Product

Resources

About