The Role of Primary Cilia in the Crosstalk between the Ubiquitin–Proteasome System and Autophagy

Wiegering, Antonia; Rüther, Ulrich; Gerhardt, Christoph

doi:10.3390/cells8030241

Cited by 20 publications

(19 citation statements)

References 166 publications

(209 reference statements)

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“…Moreover, it has been previously reported that selective degradation of ciliary proteins can also be mediated by the ubiquitin-proteasome system (UPS) to control ciliogenesis and cilia maintenance [39,40]. Autophagy and UPS are, at least partially, redundant and a crosstalk exists between them concerning their role on cilia biology [40], suggesting that the mechanism/s underlying degradation of positive and negative effectors of ciliogenesis could be intricate and depending on different cell types and/or culture conditions.…”

Section: Autophagy Controls Ciliogenesis and Cilia Lengthmentioning

confidence: 99%

The Autophagy-Cilia Axis: An Intricate Relationship

Morleo

Bazzoli

2019

Cells

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Primary cilia are microtubule-based organelles protruding from the surface of almost all vertebrate cells. This organelle represents the cell’s antenna which acts as a communication hub to transfer extracellular signals into intracellular responses during development and in tissue homeostasis. Recently, it has been shown that loss of cilia negatively regulates autophagy, the main catabolic route of the cell, probably utilizing the autophagic machinery localized at the peri-ciliary compartment. On the other side, autophagy influences ciliogenesis in a context-dependent manner, possibly to ensure that the sensing organelle is properly formed in a feedback loop model. In this review we discuss the recent literature and propose that the autophagic machinery and the ciliary proteins are functionally strictly related to control both autophagy and ciliogenesis. Moreover, we report examples of diseases associated with autophagic defects which cause cilia abnormalities, and propose and discuss the hypothesis that, at least some of the clinical manifestations observed in human diseases associated to ciliary disfunction may be the result of a perturbed autophagy.

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Section: Autophagy Controls Ciliogenesis and Cilia Lengthmentioning

confidence: 99%

The Autophagy-Cilia Axis: An Intricate Relationship

Morleo

Bazzoli

2019

Cells

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“…In addition, we also found the high expression of OFD1 in CMPTs by immunohistochemistry, which is an important inhibitor of primary cilia in cancer cells ( Wiegering et al, 2019 ). The elevation of OFD1 indicates a decrease in autophagy and the disappearance of cilia, and studies have shown a close relationship between the disappearance of cilia and tumorigenesis ( Tang et al, 2013 ).…”

Section: Discussionmentioning

confidence: 61%

“…The expression of PD-L1 (B7H1/CD274), B7H3 (CD276), and B7H4 in tissues was observed in all five patients ( Table 2 ). It is well known that PDL1, B7H3, and B7H4 are highly expressed in tumor tissues to achieve immune escape and promote tumorigenesis ( Wiegering et al, 2019 ). It is notable that PDL1, B7H3, B7H4, and other indicators are mostly expressed in mucus cells of CMPTs.…”

Section: Discussionmentioning

confidence: 99%

Ciliated Muconodular Papillary Tumors of the Lung: Distinct Molecular Features of an Insidious Tumor

et al. 2020

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Introduction Ciliated muconodular papillary tumors (CMPTs) are rare special peripheral pulmonary nodule composed of different cell proportions, characterized by papillary structures and significant alveolar mucus. Because of their rarity, underrecognized processes, the full range clinical course and histogenesis of CMPTs remains uncertain. Methods Molecular features of 5 CMPTs cases (one case with mucinous adenocarcinoma simultaneously) were observed by whole exon gene detection. The histological features of CMPTs and the development trends of three major constituent cells were studied by immunohistochemistry and PCR. Results NGS revealed 77 gene mutations in the patient’s tumor tissue and 31 mutations in the border tissue. TMB of CMPT tends to TMB of cancer tissues, and both are higher than normal tissues, CMPT share the same phylogenetic tree with cancer tissues. Moreover, PDL1, B7H3, and B7H4 were overexpressed in high columnar cells and eosinophilic ciliated cells of CMPT, tends to cancer tissues, while LAG3 and siglec15 were not found in CMPT. Conclusion The high prevalence of driver gene mutations in CMPTs, similar TMB and phylogenetic tree with cancer tissues indicate their malignant potential. Distinct molecular and immune check point features of each component support the notion that ciliated columnar cells in CMPT are insidious with immune escape.

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“…Interestingly, multiple lines of research have revealed that autophagy (Tang et al ., 2013), the ubiquitin-proteasome system (Kasahara et al ., 2014), actin remodeling factors such as LIM kinase 2 (LIMK2), testicular protein kinase (TESK1) (Kim et al ., 2015b), and serine/threonine kinases such as intestinal cell kinase (ICK) (Chaya et al ., 2014; Moon et al ., 2014) are critical for the maintenance and function of primary cilia. More recently, among these various regulators of ciliogenesis or ciliary function, interest in the bidirectional interaction between primary cilia and autophagy is increasing (Pampliega and Cuervo, 2016; Wiegering et al ., 2019). Indeed, it has been reported that cells with defective cilia show reduced autophagy (Pampliega et al ., 2013) and dysfunction of ICK known as ciliary protein leads to perturbation of ciliary signaling and autophagy (Tong et al ., 2017), which suggests that there is a close relationship between primary cilia and autophagy.…”

Section: Primary Ciliamentioning

confidence: 99%

Interplay Between Primary Cilia and Autophagy and Its Controversial Roles in Cancer

Lee

2019

Biomolecules & Therapeutics

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Primary cilia and autophagy are two distinct nutrient-sensing machineries required for maintaining intracellular energy homeostasis, either via signal transduction or recycling of macromolecules from cargo breakdown, respectively. Potential correlations between primary cilia and autophagy have been recently suggested and their relationship may increase our understanding of the pathogenesis of human diseases, including ciliopathies and cancer. In this review, we cover the current issues concerning the bidirectional interaction between primary cilia and autophagy and discuss its role in cancer with cilia defect.

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The Role of Primary Cilia in the Crosstalk between the Ubiquitin–Proteasome System and Autophagy

Cited by 20 publications

References 166 publications

The Autophagy-Cilia Axis: An Intricate Relationship

The Autophagy-Cilia Axis: An Intricate Relationship

Ciliated Muconodular Papillary Tumors of the Lung: Distinct Molecular Features of an Insidious Tumor

Interplay Between Primary Cilia and Autophagy and Its Controversial Roles in Cancer

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