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NANOG binds SPOP. 42 / 42
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"However, the cancer-associated mutation 66 PDYST 70 in the NANOG mutant increased steric hindrance and impaired its interaction with SPOP ( xref ), suggesting that the cancer-associated mutant S68Y may affect the interaction between NANOG and SPOP."
30595535
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"Since BRAF can phosphorylate NANOG at Ser68, we examined whether BRAF affects the interaction between NANOG and SPOP."
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30595538
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"Our data showed that inhibition of BRAF increased the interaction between SPOP and NANOG ( xref ) and thereby promoted NANOG ubiquitination in DU145 cells ( xref )."
30595535
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"Furthermore, in vitro phosphorylation assay demonstrated that BRAF could phosphorylate NANOG at Ser68 and the phosphorylation of NANOG at Ser68 prevented the interaction between SPOP and NANOG in vitro ( xref - xref )."
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30595538
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"The promotion of ubiquitination and subsequent UPS-dependent degradation of Nanog is facilitated by SPOP, which relies on the interaction between Nanog-SPOP involving the MATH structural domain of SPOP and the SPOP-binding consensus degron of NANOG. xref , xref "
40034124
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"Taken together, these results demonstrate that BRAF directly phosphorylates NANOG at Ser68 and increases the self-renewal capacity and cell proliferation of PCa cells by impairing the interaction between SPOP and NANOG."
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"In addition, SPOP mediated NANOG degradation is controlled by the AMPK-BRAF signal axis through the phosphorylation of NANOG at Ser68, which blocked the interaction between SPOP and NANOG."
30595535
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"Clinically, cancer-associated mutations in the MATH domain of SPOP disrupt the interaction between SPOP and NANOG, thereby preventing SPOP-mediated destruction of NANOG, stabilizing NANOG from AMPK-BRAF-signaling-axis-induced phosphorylation, and consequently promoting the maintenance of PCa stem-like cells."
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"SPOP-Q360* repressed levels of NANOG and other downstream proteins to a much weaker extent than SPOP-WT (Fig. 7d), and these results were associated with impaired interaction between SPOP and NANOG, as well as impaired ubiquitination of NANOG (Fig. 7e, f)."
31624231
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"In addition, XinboWang et al. have reported that SPOP-mediated Nanog degradation is regulated by the AMPK-BRAF signal pathway by Nanog phosphorylation, which inhibits the interaction between SPOP and [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35337852
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"In addition, SPOP-mediated NANOG degradation is controlled by AMPK-BRAF signal axis through the phosphorylation of NANOG at Ser68, which blocked the interaction between SPOP and NANOG."
30595535
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"The cancer-associated NANOG S68Y mutant is refractory for SPOP-mediated degradation since NANOG Ser68 is required for the direct interaction between SPOP and NANOG."
30595535
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"Notably, we found that Nanog specifically interacted with SPOP, but not other Cullin 3-based E3 ligase adaptor proteins including Keap1, KLHL2, KLHL3, KLHL12, KLHL20, or COP1/ DET1, a Cullin 4-based E3 ligase substrate adaptor protein ( xref ; xref ) ( xref and xref )."
30595538
reach
"In addition, XinboWang et al. have reported that SPOP-mediated Nanog degradation is regulated by the AMPK-BRAF signal pathway by Nanog phosphorylation, which inhibits the interaction between SPOP and [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35337852
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"Moreover, our data showed that NANOG specifically interacts with SPOP, but not other Cullin3-based E3 ligase adaptor proteins ( xref )."
30595535
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"Next, we determined the molecular basis of the interaction between NANOG and SPOP."
30595535
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"Moreover, SPOP specifically interacted with Nanog both in vitro and in cells ( xref – xref ) but not with other stem cell determining factors such as Oct4, Sox2, and Klf4 in cells ( xref )."
30595538
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"Our data indicated that SPOP specifically interacts with NANOG, but not other stem cell transcriptional factors, including OCT4, SOX2, and KLF4 ( xref )."
30595535
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"Notably, the interaction between endogenous SPOP and NANOG could be readily detected in PCa cells ( xref and xref ) and E14 mESCs ( xref )."
30595535
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"Notably, we observed that deletion of the MATH domain could disrupt SPOP interaction with Nanog and abrogate SPOP-mediated Nanog destruction ( xref and xref )."
30595538
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"Importantly, deleting the putative motif 66PDSST 70 (ΔPDSST) impaired the interaction between Nanog and SPOP both in cells and in vitro ( xref , xref , and xref ), leading to acquired resistance to SPOP-mediated destruction ( xref – xref ) and poly-ubiquitination in cells and in vitro ( xref and xref )."
30595538
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"Our data showed that wild-type SPOP directly interacted with NANOG whereas the absence of the MATH domain completely abrogated the binding in vitro and in vivo ( xref and xref )."
30595535
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"We then examined whether the putative SBC motif is involved in the interaction between SPOP and NANOG."
30595535
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"We next explored whether the residues located in the SBC motif involve in the interaction between NANOG and SPOP."
30595535
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"Given that Pin1 recognizes the pSer/pThr-Pro motif and two SP sites (S65 and S71) located nearby the SPOP binding motif on the Nanog protein ( xref ), we speculated that Pin1 might disrupt Nanog interaction with SPOP through binding these two SP sites."
30595538
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"Notably, we found that well-characterized Pin1 inhibitors, PiB ( xref ; xref ; xref ) and Juglone ( xref ), could promote SPOP-mediated Nanog degradation ( xref and xref ) through elevating Nanog interaction with SPOP in cells ( xref and xref )."
30595538
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"To confirm this result, we examined the interaction between NANOG S68Y and SPOP."
30595535
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"In keeping with this notion, we found that Pin1 WT (Pin1-WT), but not its enzymatically inactive mutant W34A/K63A ( xref ), suppressed SPOP-mediated degradation of Nanog largely through disrupting the interaction between SPOP and Nanog in cells ( xref and xref )."
30595538
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"In prostate cancer, tumor suppressor SPOP interacts with Nanog and promotes Nanog poly-ubiquitination and subsequent degradation, but Pin1 functions as an upstream Nanog regulator and impairs its recognition by SPOP, stabilizing Nanog to promote the cancer stem cell traits and tumor progression ( xref )."
32296699
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"SPOP-mediated NANOG degradation is controlled by the AMPK-BRAF signaling axis through the phosphorylation of NANOG at Ser68, which blocks the interaction between SPOP and NANOG [ xref , xref ]."
37047234
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"Moreover, inhibition of AMPK abrogated the interaction between SPOP and NANOG, while activation of AMPK strengthened the association between SPOP and NANOG ( xref and xref )."
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