Interactome Analysis of KIN (Kin17) Shows New Functions of This Protein

Abstract

KIN (Kin17) protein is overexpressed in a number of cancerous cell lines, and is therefore considered a possible cancer biomarker. It is a well-conserved protein across eukaryotes and is ubiquitously expressed in all cell types studied, suggesting an important role in the maintenance of basic cellular function which is yet to be well determined. Early studies on KIN suggested that this nuclear protein plays a role in cellular mechanisms such as DNA replication and/or repair; however, its association with chromatin depends on its methylation state. In order to provide a better understanding of the cellular role of this protein, we investigated its interactome by proximity-dependent biotin identification coupled to mass spectrometry (BioID-MS), used for identification of protein–protein interactions. Our analyses detected interaction with a novel set of proteins and reinforced previous observations linking KIN to factors involved in RNA processing, notably pre-mRNA splicing and ribosome biogenesis. However, little evidence supports that this protein is directly coupled to DNA replication and/or repair processes, as previously suggested. Furthermore, a novel interaction was observed with PRMT7 (protein arginine methyltransferase 7) and we demonstrated that KIN is modified by this enzyme. This interactome analysis indicates that KIN is associated with several cell metabolism functions, and shows for the first time an association with ribosome biogenesis, suggesting that KIN is likely a moonlight protein.

A chemical probe to modulate human GID4 Pro/N-degron interactions

“…Interactors that were lost upon PFI-7 treatment included RNA helicases DDX17, DDX21, and DDX50 that have previously been reported to associate with the CTLH complex 16,18,34,36 , and that we now show are GID4-dependent interactors. Indeed, many of the direct GID4 interactors are nucleolar proteins including DDX21 39 , DDX50 40 , and KIN 41 , among others. This points to possible nucleolar-specific functions of the CTLH complex that have been suggested previously 36 and remain to be elucidated further.…”

“…Intriguingly, PFI-7 treatment decreased levels of several proteins including KIN. KIN is a DNA and RNA binding protein implicated in ribosome biogenesis whose interactome shares several interactors with GID4, including DDX50 41 . There are several plausible explanations for how GID4 antagonism by PFI-7 might lead to decreased protein abundance.…”

KIN17 promotes cell migration and invasion through stimulating the TGF‐β/Smad2 pathway in hepatocellular carcinoma

“…In past studies, we didn't discover how KIN17 regulates EMT in tumor cells. However, through the protein–protein interaction network and bioinformatics of KIN17, we have found that KIN17 is likely to interact with Smad2 31 . Smad2 is an important factor of TGF‐β pathway, so we speculated that KIN17 induced EMT through the TGF‐β/Smad2 pathway 18 .…”

“…However, through the protein-protein interaction network and bioinformatics of KIN17, we have found that KIN17 is likely to interact with Smad2. 31 Smad2 is an important factor of TGF-β pathway, so we speculated that KIN17 induced EMT through the TGF-β/Smad2 pathway. 18 Here, we first verified that the expression of Smad2 and P-Smad2 protein changed with the change After 24 h, we observed that the cells migration and invasion ability, and the expression levels of p-Smad2 and EMT-related proteins were rescued.…”

Roles and regulatory mechanisms of KIN17 in cancers (Review)

“…New interactions between KIN17 and other proteins have also been found, particularly proteins related to RNA processing, such as certain proteins associated with pre-mRNA splicing and ribosome biogenesis (Fig. 3) (29).…”