HACE1 mediated K27 ubiquitin linkage leads to YB-1 protein secretion

Palicharla, Vivek Reddy; Maddika, Subbareddy

doi:10.1016/j.cellsig.2015.09.001

Cited by 56 publications

(37 citation statements)

References 28 publications

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“…We demonstrated in this report that HACE1 interacts with FN, promotes its K27 ubiquination and regulates its secretion. In agreement with our data, HACE1 has been recently reported to promote K27 ubiquitination of YB1 and to regulate its secretion [30]. Because FN is a large protein, we have not been able to identify the site of K27 ubiquitination, but the inhibition of FN secretion by the forced expression of K27R ubiquitin strongly supports the hypothesis that HACE1 regulates FN secretion through its K27 ubiquitination.…”

Section: Discussionsupporting

confidence: 89%

Uncovering and deciphering the pro-invasive role of HACE1 in melanoma cells

et al. 2018

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HACE1 is an E3 ubiquitin ligase described as a tumour suppressor because HACE1-knockout mice develop multi-organ, late-onset cancers and because HACE1 expression is lost in several neoplasms, such as Wilms' tumours and colorectal cancer. However, a search of public databases indicated that HACE1 expression is maintained in melanomas. We demonstrated that HACE1 promoted melanoma cell migration and adhesion in vitro and was required for mouse lung colonisation by melanoma cells in vivo. Transcriptomic analysis of HACE1-depleted melanoma cells revealed an inhibition of ITGAV and ITGB1 as well changes in other genes involved in cell migration. We revealed that HACE1 promoted the K27 ubiquitination of fibronectin and regulated its secretion. Secreted fibronectin regulated ITGAV and ITGB1 expression, as well as melanoma cell adhesion and migration. Our findings disclose a novel molecular cascade involved in the regulation of fibronectin secretion, integrin expression and melanoma cell adhesion. By controlling this cascade, HACE1 displays pro-tumoural properties and is an important regulator of melanoma cell invasive properties.

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Section: Discussionsupporting

confidence: 89%

Uncovering and deciphering the pro-invasive role of HACE1 in melanoma cells

et al. 2018

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“…The multi-functional YB-1 protein has widespread DNA/RNA binding activities [56] and has historically been thought of as a cold shock protein [56]. Interestingly however, YB-1 can be secreted from mesangial and immune cells after cytokine stimulation via a non-classical mechanism that involves ubiquitin E3 ligase HACE-1 mediated K27 ubiquitination and association with the Tumor Susceptibility Gene 101 (TSG101) [57, 58]. In turn, secreted YB-1 has been found to specifically interact with Notch3 EGF repeats and to control Notch3 downstream signaling, but not Notch1 signaling [59, 60].…”

Section: Direct Ecm-notch Interactions That Control Notch Signalingmentioning

confidence: 99%

Notch: A multi-functional integrating system of microenvironmental signals

LaFoya

Munroe

Mia

et al. 2016

Developmental Biology

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The Notch signaling cascade is an evolutionarily ancient system that allows cells to interact with their microenvironmental neighbors through direct cell-cell interactions, thereby directing a variety of developmental processes. Recent research is discovering that Notch signaling is also responsive to a broad variety of stimuli beyond cell-cell interactions, including: ECM composition, crosstalk with other signaling systems, shear stress, hypoxia, and hyperglycemia. Given this emerging understanding of Notch responsiveness to microenvironmental conditions, it appears that the classical view of Notch as a mechanism enabling cell-cell interactions, is only a part of a broader function to integrate microenvironmental cues. In this review, we summarize and discuss published data supporting the idea that the full function of Notch signaling is to serve as an integrator of microenvironmental signals thus allowing cells to sense and respond to a multitude of conditions around them.

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“…Despite intensive studies, little is known about the molecular recognition of K27‐linked Ubs, which has recently been implicated in celluar processes including lysosomal localization, mitochondrial autophagy, protein secretion, DNA repair, and autoimmunity . The bottleneck is that the enzymatic reconstitution of K27 Ubs remains impossible, so chemical methods are needed .…”

Section: Figurementioning

confidence: 99%

Chemical Protein Synthesis Enabled Mechanistic Studies on the Molecular Recognition of K27‐linked Ubiquitin Chains

et al. 2019

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New synthetic strategies that exploited the strengths of both chemoselective ligation and recombinant protein expression were developed to prepare K27 di-ubiquitins (diUb), which enabled mechanistic studies on the molecular recognition of K27-linked Ubs by single-molecule Fçrster resonance energy transfer (smFRET) and X-ray crystallography.The results revealed that free K27 diUb adopted acompact conformation, whereas upon binding to UCHL3, K27 diUb was remodeled to an open conformation. The K27 isopeptide bond remained rigidly buried inside the diUb moiety during binding,a ni nteresting unique structural feature that may explain the distinctive biological function of K27 Ub chains.

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HACE1 mediated K27 ubiquitin linkage leads to YB-1 protein secretion

Cited by 56 publications

References 28 publications

Uncovering and deciphering the pro-invasive role of HACE1 in melanoma cells

Uncovering and deciphering the pro-invasive role of HACE1 in melanoma cells

Notch: A multi-functional integrating system of microenvironmental signals

Chemical Protein Synthesis Enabled Mechanistic Studies on the Molecular Recognition of K27‐linked Ubiquitin Chains

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