Protein interaction screening identifies <scp>SH</scp>3<scp>RF</scp>1 as a new regulator of <scp>FAT</scp>1 protein levels

Bock, Charles E. de; Hughes, Michael R.; Snyder, Kimberly; Alley, Steven; Sadeqzadeh, Elham; Dun, Matthew D.; McNagny, Kelly M.; Molloy, Timothy J.; Hondermarck, Hubert; Thorne, Rick F.

doi:10.1002/1873-3468.12569

Cited by 5 publications

(4 citation statements)

References 51 publications

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“…Sh3rf1 is an SH3 domain-containing scaffold molecule necessary for JNK signaling 43 . Sh3rf1 can also function as an E3 ubiquitin ligase to regulate additional pathways 44,45 . Importantly, the scaffold function of Sh3rf1 is independent of its E3 ligase activity, and Sh3rf1 with deleted RING finger domain (SH3RF1 ΔRing ) can still support JNK signaling 46,47 .…”

Section: Resultsmentioning

confidence: 99%

Oncogenic activation of PI3K induces progenitor cell differentiation to suppress epidermal growth

2018

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Oncogenic lesions are surprisingly common in morphologically and functionally normal human skin, however, the cellular and molecular mechanisms that suppress their cancer-driving potential to maintain tissue homeostasis are unknown. By employing assays for direct and quantitative assessment of cell fate choices in vivo , we show that oncogenic activation of PI3K/AKT, the most commonly activated oncogenic pathway in cancer, promotes differentiation and cell-cycle exit of epidermal progenitors. As a result, oncogenic PI3K/AKT activated epidermis exhibits growth disadvantage even though its cells are more proliferative. To uncover the underlying mechanism behind oncogene-induced differentiation, we conduct a series of genetic screens in vivo , and identify an AKT substrate SH3RF1 as a specific promoter of epidermal differentiation that has no effect on proliferation. Our study provides evidence for a direct, cell autonomous mechanism that can suppresses progenitor cell renewal and block clonal expansion of epidermal cells bearing a common and activating mutation in Pik3ca.

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Section: Resultsmentioning

confidence: 99%

Oncogenic activation of PI3K induces progenitor cell differentiation to suppress epidermal growth

2018

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“…It is also involved in the regulation of Ca 2 + homeostasis by decreasing the surface levels of the endoplasmic reticulum calcium sensor STIM1 43 . As CIB1 is a positive transcriptional regulator 44 and SH3RF1 is a negative post-transcriptional regulator 45 , CIB1 may act as a transcriptional co-activator binding with ONECUT3, and SH3RF1 may function as a negative feedback regulator interacting with ONECUT3. Furthermore, the potential drugs sensitive to ONECUT3 high PDACs with high stemness were screened using CTRP and GDSC.…”

Section: Resultsmentioning

confidence: 99%

Identification of ONECUT3 as a stemness-related transcription factor regulating NK cell-mediated immune evasion in pancreatic cancer

Shi,

Tsang,

Yang

et al. 2023

Sci Rep

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Pancreatic ductal adenocarcinoma (PDAC) has a dismal response to the current T cell-based immunotherapies, which is attributed to intratumoral heterogeneity caused by PDAC stem cells and lack of major histocompatibility complex class I required for neoantigen presentation. Although this scenario makes natural killer (NK) cells attractive candidates for immunotherapeutic agents targeting MHC-I-deficient cancer stem cells in heterogeneous PDACs, little is known about PDAC stem cell immunology. In our study, PDAC-specific datasets from public databases were collected for in-depth bioinformatic analysis. We found that the abundance of PDAC stemness negatively influenced the infiltration of NK cells and identified the transcription factor ONECUT3 enriched in PDACs with high stemness index scores and Pan-cancer Stemness Signature levels. A series of NK cell-targeted inhibitory immune checkpoints were highly expressed in ONECUT3high PDACs. The patient group with high levels of ONECUT3 expression had a high risk of poor overall survival, even if accompanied by high infiltration of NK cells. Furthermore, the prostanoid metabolic process was enriched in ONECUT3high PDACs with high levels of NK cell-targeted inhibitory immune checkpoints. ONECUT3 enriched in high-stemness PDACs possessed the potential to transcriptionally regulate the prostanoid metabolism-related genes. Our study reveals ONECUT3 as a candidate stemness-related transcription factor regulating NK cell-targeted inhibitory immune checkpoints in PDAC. ONECUT3-mediated prostanoid metabolism may regulate cancer stemness and immune evasion in PDAC. Synergistic inhibition of prostanoid metabolism may improve the efficacy of NK cell-based immunotherapies targeting intratumoral heterogeneity caused by PDAC stem cells.

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“…Family protocadherin gamma subfamily C is correlated to protocadherin production. The family CD179 antigen-like family member A is interact with protocadherin fat 1 [ 30 ]. More interestingly, researchers found that cooperation between olfactory receptor genes and protocadherin genes is correlated with obesity in human [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Similar proteome expression profiles of the aggregated lymphoid nodules area and Peyer’s patches in Bactrian camel

Cheng,

Ren,

Wang

et al. 2023

BMC Genomics

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Background The presence of Aggregated Lymphoid Nodules Area (ALNA) is a notable anatomical characteristic observed in the abomasum of Bactrian camels. This area is comprised of two separate regions, namely the Reticular Mucosal Folds Region (RMFR) and the Longitudinal Mucosal Folds Region (LMFR). The histological properties of ALNA exhibit significant similarities to those of Peyer’s patches (PPs) found in the gastrointestinal system. The functional characteristics of ALNA were examined in relation to mucosal immunity in the gastrointestinal system. Results We used iTRAQ-based proteomic analysis on twelve Bactrian camels to measure the amount of proteins expressed in ALNA. In the experiment, we sampled the RMFR and LMFR separately from the ALNA and compared their proteomic quantification results with samples from the PPs. A total of 1253 proteins were identified, among which 39 differentially expressed proteins (DEPs) were found between RMFR and PPs, 33 DEPs were found between LMFR and PPs, and 22 DEPs were found between LMFR and RMFR. The proteins FLNA, MYH11, and HSPB1 were chosen for validation using the enzyme-linked immunosorbent assay (ELISA), and the observed expression profiles were found to be in agreement with the results obtained from the iTRAQ study. The InnateDB database was utilized to get data pertaining to immune-associated proteins in ALNA. It was observed that a significant proportion, specifically 76.6%, of these proteins were found to be associated with the same orthogroups as human immune-related genes. These proteins are acknowledged to be associated with a diverse range of functions, encompassing the uptake, processing and presentation of antigens, activation of lymphocytes, the signaling pathways of T-cell and B-cell receptors, and the control of actin polymerization. Conclusions The experimental results suggest that there are parallels in the immune-related proteins found in ALNA and PPs. Although there are variations in the structures of LMFR and RMFR, the proteins produced in both structures exhibit a high degree of similarity and perform comparable functions in the context of mucosal immune responses.

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Protein interaction screening identifies SH3RF1 as a new regulator of FAT1 protein levels

Cited by 5 publications

References 51 publications

Oncogenic activation of PI3K induces progenitor cell differentiation to suppress epidermal growth

Oncogenic activation of PI3K induces progenitor cell differentiation to suppress epidermal growth

Identification of ONECUT3 as a stemness-related transcription factor regulating NK cell-mediated immune evasion in pancreatic cancer

Similar proteome expression profiles of the aggregated lymphoid nodules area and Peyer’s patches in Bactrian camel

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