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NANOG binds SPOP. 46 / 46
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"Since BRAF can phosphorylate NANOG at Ser68, we examined whether BRAF affects the interaction between NANOG and SPOP."
30595535
sparser
"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
sparser
"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 )."
30595535
sparser
"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
biogrid
No evidence text available
30595538
sparser
"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."
30595535
biogrid
No evidence text available
30595538
reach
"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
sparser
"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."
30595535
biogrid
No evidence text available
31624231
reach
"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
biogrid
No evidence text available
30595538
sparser
"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
sparser
"Pin1 and the AMPK-BRAF signaling axis were identified as upstream negative regulators of SPOP, blocking the interaction between SPOP and Nanog."
40521202
biogrid
No evidence text available
31624231
biogrid
No evidence text available
26687479
biogrid
No evidence text available
30595535
biogrid
No evidence text available
30595535
sparser
"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
sparser
"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
sparser
"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
sparser
"Our data indicated that SPOP specifically interacts with NANOG, but not other stem cell transcriptional factors, including OCT4, SOX2, and KLF4 ( xref )."
30595535
biogrid
No evidence text available
30595535
sparser
"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
biogrid
No evidence text available
30595535
biogrid
No evidence text available
30595535
sparser
"Notably, the interaction between endogenous SPOP and NANOG could be readily detected in PCa cells ( xref and xref ) and E14 mESCs ( xref )."
30595535
sparser
"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
sparser
"Targeting the SPOP-NANOG axis presents a promising therapeutic strategy for pancreatic cancer."
40521202
sparser
"Moreover, our data showed that NANOG specifically interacts with SPOP, but not other Cullin3-based E3 ligase adaptor proteins ( xref )."
30595535
sparser
"Next, we determined the molecular basis of the interaction between NANOG and SPOP."
30595535
sparser
"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
sparser
"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
sparser
"We then examined whether the putative SBC motif is involved in the interaction between SPOP and NANOG."
30595535
sparser
"We next explored whether the residues located in the SBC motif involve in the interaction between NANOG and SPOP."
30595535
sparser
"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
sparser
"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
sparser
"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
sparser
"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
sparser
"To confirm this result, we examined the interaction between NANOG S68Y and SPOP."
30595535
sparser
"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
sparser
"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
sparser
"Through molecular docking analysis, we identified specific amino acid residues involved in the interaction between the SPOP and NANOG proteins."
40657370
sparser
"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 )."
30595535
sparser
"Additionally, the 94th PRO residue of SPOP interacts with the 124th LYS residue of NANOG via a hydrogen bond with a length of 3.3 Å. The 62nd ASN and 63rd ASP residues of SPOP form hydrogen bonds with the 180th SER and 181st TYR residues of NANOG, with bond lengths of 2.1 Å and 2.6 Å, respectively (Figure xref A)."
40657370