SCYL1BP1 has Tumor-suppressive Functions in Human Lung Squamous Carcinoma Cells by Regulating Degradation of MDM2

Yang, Zhiping; Xie, Ying; Ling, Dan-yan; Li, Jingrui; Jin, Jianhua; Fan, Yun; Ji, Zheng; Wu, Wanxin

doi:10.7314/apjcp.2014.15.17.7467

Cited by 6 publications

(6 citation statements)

References 32 publications

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“…Interestingly, GORAB has been linked to the regulation of TRP53 (p53) expression during neurite outgrowth ( Liu et al. , 2012 ) and tumor cell growth in vitro ( Hu et al , 2012 ; Yang et al , 2014 ), in which GORAB acts in MDM2-mediated polyubiquitination and proteasome degradation of p53 ( Yan et al , 2010 ; Zhang et al , 2005 ). While regulating p53 stability by GORAB unlikely plays a significant role during epidermal morphogenesis, it remains to be determined whether GORAB is involved in post-natal skin homeostasis by regulating the level of p53 at the post-translational level.…”

Section: Discussionmentioning

confidence: 99%

Gorab Is Required for Dermal Condensate Cells to Respond to Hedgehog Signals during Hair Follicle Morphogenesis

Liu

Snedecor

Choi

et al. 2016

Journal of Investigative Dermatology

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GORAB is a golgin that localizes predominantly at the Golgi apparatus and physically interacts with small GTPases. GORAB is ubiquitously expressed in mammalian tissues, including the skin. However, the biological function of this golgin in skin is unknown. Here, we report that disrupting the expression of the Gorab gene in mice results in hair follicle morphogenesis defects that were characterized by impaired follicular keratinocyte differentiation. This hair follicle phenotype was associated with markedly suppressed hedgehog (Hh) signaling pathway in dermal condensates in vivo. Gorab-deficient dermal mesenchymal cells also displayed significantly reduced capability to respond to Hh pathway activation in vitro. Furthermore, we found that the formation of primary cilium, a cellular organelle that is essential for the Hh pathway, was impaired in mutant dermal papilla cells, suggesting that Gorab may be required for the Hh pathway through facilitating the formation of primary cilia. Thus, data obtained from this study provided insight onto the biological functions of Gorab during embryonic morphogenesis of skin in which Hh signaling and primary cilia exert important functions.

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Section: Discussionmentioning

confidence: 99%

Gorab Is Required for Dermal Condensate Cells to Respond to Hedgehog Signals during Hair Follicle Morphogenesis

Liu

Snedecor

Choi

et al. 2016

Journal of Investigative Dermatology

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“…This protein is an endothelial cell surface receptor that displays several functions associated with host defence [28,29]. SCYL1BP1 encodes SCY1-like 1-binding protein 1, a regulator of the p53 pathway with tumour-suppressive function [30][31][32]. API5 encodes the protein apoptosis inhibitor 5, which is reported to be a suppressor of apoptosis and to play a key role in tumour progression [33,34].…”

Section: Discussionmentioning

confidence: 99%

Common variants in or near ZNRF1, COLEC12, SCYL1BP1 and API5 are associated with diabetic retinopathy in Chinese patients with type 2 diabetes

et al. 2015

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Aims/hypothesis Three recent genome-wide association studies (GWAS) identified several single-nucleotide polymorphisms (SNPs) with modest effects on diabetic retinopathy in Mexican-American and white patients with diabetes. This study aimed to evaluate the effects of these variants on diabetic retinopathy in Chinese patients with type 2 diabetes. Methods A total of 1,972 patients with type 2 diabetes were recruited to this study, including 819 patients with diabetic retinopathy and 1,153 patients with diabetes of ≥5 years duration but without retinopathy. Forty SNPs associated with diabetic retinopathy in three GWAS were genotyped. Fundus photography was performed to diagnose and classify diabetic retinopathy. Results rs17684886 in ZNRF1 and rs599019 near COLEC12 were associated with diabetic retinopathy (OR 0.812, p=0.0039 and OR 0.835, p=0.0116, respectively) and with the severity of diabetic retinopathy (p=0.0365 and p=0.0252, respectively, for trend analysis). Sub-analysis in patients with diabetic retinopathy revealed that rs6427247 near SCYL1BP1 (also known as GORAB) and rs899036 near API5 were associated with severe diabetic retinopathy (OR 1.368, p=0.0333 and OR 0.340, p=0.0005, respectively). The associations between rs6427247 and rs899036 and severe diabetic retinopathy became more evident after a meta-analysis of published GWAS data (OR 1.577, p=2.01×10 −4 for rs6427247; OR 0.330, p=5.84×10 −7 for rs899036). Conclusions/interpretation We determined that rs17684886 and rs599019 are associated with diabetic retinopathy and that rs6427247 and rs899036 are associated with severe diabetic retinopathy in Chinese patients with type 2 diabetes.

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“…1,2 GORAB is also implicated in bone and hair follicle formation, 3,4 neurite outgrowth, 5 sciatic nerve regeneration, 6 and tumor cell growth. [7][8][9] GORAB is expressed in the lung. 1,3,6 We found that homozygous neonates of Gorab knockout (Gorab −/− ) mouse models exhibited severe breathing difficulties and fully penetrant neonatal lethality, 3 suggesting that GORAB plays a critical role in the embryonic morphogenesis of the respiratory or the cardiovascular system.…”

Section: Introductionmentioning

confidence: 99%

“…GORAB physically interacts with RAB6 and ARF5, and is believed to function in intracellular trafficking . GORAB is also implicated in bone and hair follicle formation, neurite outgrowth, sciatic nerve regeneration, and tumor cell growth …”

Section: Introductionmentioning

confidence: 99%

GORAB promotes embryonic lung maturation through antagonizing AKT phosphorylation, versican expression, and mesenchymal cell migration

et al. 2020

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Embryonic development of the alveolar sac of the lung is dependent upon multiple signaling pathways to coordinate cell growth, migration, and the formation of the extracellular matrix. Here, we identify GORAB as a regulator of embryonic alveolar sac formation as genetically disrupting the Gorab gene in mice resulted in fatal saccular maturation defects characterized by a thickened lung mesenchyme. This abnormality is not associated with impairments in cellular proliferation and death, but aberrantly increased protein kinase B (AKT) phosphorylation, elevated Vcan transcription, and enhanced migration of mesenchymal fibroblasts. Genetically augmenting PDGFRα, a potent activator of AKT in lung mesenchymal cells, recapitulated the alveolar phenotypes, whereas disrupting PDGFRα partially rescued alveolar phenotypes in Gorab‐deficient mice. Overexpressing or suppressing Vcan in primary embryonic lung fibroblasts could, respectively, mimic or attenuate alveolar sac‐like phenotypes in a co‐culture model. These findings suggest a role of GORAB in negatively regulating AKT phosphorylation, the expression of Vcan, and the migration of lung mesenchyme fibroblasts, and suggest that alveolar sac formation resembles a patterning event that is orchestrated by molecular signaling and the extracellular matrix in the mesenchyme.

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SCYL1BP1 has Tumor-suppressive Functions in Human Lung Squamous Carcinoma Cells by Regulating Degradation of MDM2

Cited by 6 publications

References 32 publications

Gorab Is Required for Dermal Condensate Cells to Respond to Hedgehog Signals during Hair Follicle Morphogenesis

Gorab Is Required for Dermal Condensate Cells to Respond to Hedgehog Signals during Hair Follicle Morphogenesis

Common variants in or near ZNRF1, COLEC12, SCYL1BP1 and API5 are associated with diabetic retinopathy in Chinese patients with type 2 diabetes

GORAB promotes embryonic lung maturation through antagonizing AKT phosphorylation, versican expression, and mesenchymal cell migration

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