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PubMed:27226552 JSONTXT

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PubMed_ArguminSci

Id Subject Object Predicate Lexical cue
T1 207-362 DRI_Background denotes The protein kinase casein kinase 2 (CK2) is a pleiotropic and constitutively active kinase that plays crucial roles in cellular proliferation and survival.
T2 363-598 DRI_Outcome denotes Overexpression of CK2, particularly the α catalytic subunit (CK2α, CSNK2A1), has been implicated in a wide variety of cancers and is associated with poorer survival and resistance to both conventional and targeted anticancer therapies.
T3 599-706 DRI_Outcome denotes Here, we found that CK2α protein is elevated in melanoma cell lines compared with normal human melanocytes.
T4 707-851 DRI_Approach denotes We then tested the involvement of CK2α in drug resistance to Food and Drug Administration-approved single agent targeted therapies for melanoma.
T5 852-1060 DRI_Outcome denotes In BRAF mutant melanoma cells, ectopic CK2α decreased sensitivity to vemurafenib (BRAF inhibitor), dabrafenib (BRAF inhibitor), and trametinib (MEK inhibitor) by a mechanism distinct from that of mutant NRAS.
T6 1061-1131 DRI_Background denotes Conversely, knockdown of CK2α sensitized cells to inhibitor treatment.
T7 1132-1145 REPLACED denotes CK2α-mediated
T8 1154-1243 DRI_Background denotes kinase inhibitor resistance was tightly linked to its maintenance of ERK phosphorylation.
T9 1244-1257 DRI_Outcome denotes We found that
T10 1284-1417 DRI_Outcome denotes regulates the ERK-specific phosphatase dual specificity phosphatase 6 (DUSP6) in a kinase dependent-manner, decreasing its abundance.
T11 1418-1598 DRI_Outcome denotes However, we unexpectedly showed, by using a kinase-inactive mutant of CK2α, that RAF-MEK inhibitor resistance did not rely on CK2α kinase catalytic function, and both wild-type and
T12 1620-1682 DRI_Outcome denotes maintained ERK phosphorylation upon inhibition of BRAF or MEK.
T13 1683-1706 DRI_Outcome denotes That both wild-type and
T14 1728-1879 DRI_Outcome denotes bound equally well to the RAF-MEK-ERK scaffold kinase suppressor of Ras 1 (KSR1) suggested that CK2α increases KSR facilitation of ERK phosphorylation.
T15 1880-1995 DRI_Outcome denotes Accordingly, CK2α did not cause resistance to direct inhibition of ERK by the ERK1/2-selective inhibitor SCH772984.
T16 1996-2127 DRI_Outcome denotes Our findings support a kinase-independent scaffolding function of CK2α that promotes resistance to RAF- and MEK-targeted therapies.

sentences

Id Subject Object Predicate Lexical cue
T1 0-206 Sentence denotes Protein Kinase CK2α Maintains Extracellular Signal-regulated Kinase (ERK) Activity in a CK2α Kinase-independent Manner to Promote Resistance to Inhibitors of RAF and MEK but Not ERK in BRAF Mutant Melanoma.
T2 207-362 Sentence denotes The protein kinase casein kinase 2 (CK2) is a pleiotropic and constitutively active kinase that plays crucial roles in cellular proliferation and survival.
T3 363-598 Sentence denotes Overexpression of CK2, particularly the α catalytic subunit (CK2α, CSNK2A1), has been implicated in a wide variety of cancers and is associated with poorer survival and resistance to both conventional and targeted anticancer therapies.
T4 599-706 Sentence denotes Here, we found that CK2α protein is elevated in melanoma cell lines compared with normal human melanocytes.
T5 707-851 Sentence denotes We then tested the involvement of CK2α in drug resistance to Food and Drug Administration-approved single agent targeted therapies for melanoma.
T6 852-1060 Sentence denotes In BRAF mutant melanoma cells, ectopic CK2α decreased sensitivity to vemurafenib (BRAF inhibitor), dabrafenib (BRAF inhibitor), and trametinib (MEK inhibitor) by a mechanism distinct from that of mutant NRAS.
T7 1061-1131 Sentence denotes Conversely, knockdown of CK2α sensitized cells to inhibitor treatment.
T8 1132-1243 Sentence denotes CK2α-mediated RAF-MEK kinase inhibitor resistance was tightly linked to its maintenance of ERK phosphorylation.
T9 1244-1417 Sentence denotes We found that CK2α post-translationally regulates the ERK-specific phosphatase dual specificity phosphatase 6 (DUSP6) in a kinase dependent-manner, decreasing its abundance.
T10 1418-1682 Sentence denotes However, we unexpectedly showed, by using a kinase-inactive mutant of CK2α, that RAF-MEK inhibitor resistance did not rely on CK2α kinase catalytic function, and both wild-type and kinase-inactive CK2α maintained ERK phosphorylation upon inhibition of BRAF or MEK.
T11 1683-1879 Sentence denotes That both wild-type and kinase-inactive CK2α bound equally well to the RAF-MEK-ERK scaffold kinase suppressor of Ras 1 (KSR1) suggested that CK2α increases KSR facilitation of ERK phosphorylation.
T12 1880-1995 Sentence denotes Accordingly, CK2α did not cause resistance to direct inhibition of ERK by the ERK1/2-selective inhibitor SCH772984.
T13 1996-2127 Sentence denotes Our findings support a kinase-independent scaffolding function of CK2α that promotes resistance to RAF- and MEK-targeted therapies.

mondo_disease

Id Subject Object Predicate Lexical cue mondo_id
T1 197-205 Disease denotes Melanoma http://purl.obolibrary.org/obo/MONDO_0005105
T2 647-655 Disease denotes melanoma http://purl.obolibrary.org/obo/MONDO_0005105
T3 842-850 Disease denotes melanoma http://purl.obolibrary.org/obo/MONDO_0005105
T4 867-875 Disease denotes melanoma http://purl.obolibrary.org/obo/MONDO_0005105

HP-phenotype

Id Subject Object Predicate Lexical cue hp_id
T1 197-205 Phenotype denotes Melanoma HP:0002861
T2 647-655 Phenotype denotes melanoma HP:0002861
T3 749-764 Phenotype denotes drug resistance HP:0020174
T4 842-850 Phenotype denotes melanoma HP:0002861
T5 867-875 Phenotype denotes melanoma HP:0002861

NCBITAXON

Id Subject Object Predicate Lexical cue db_id
T1 688-693 OrganismTaxon denotes human 9606

Anatomy-UBERON

Id Subject Object Predicate Lexical cue uberon_id
T1 30-43 Body_part denotes Extracellular http://purl.obolibrary.org/obo/GO_0005576
T2 694-705 Body_part denotes melanocytes http://purl.obolibrary.org/obo/CL_0000148

CL-cell

Id Subject Object Predicate Lexical cue cl_id
T1 694-705 Cell denotes melanocytes http://purl.obolibrary.org/obo/CL:0000148