Mechanistic model of KLF11-mediated tumor suppression and its antagonism by an oncogenic pathway

Mechanistic model of KLF11-mediated tumor suppression and its antagonism by an oncogenic pathway. KLF11 binds to the GC-rich consensus sequences in the promoter region of cPLA2α, the key rate-limiting enzyme of the oncogenic PGE2 cascade. A, KLF11 represses the cPLA2α promoter by recruiting the chromatin remodeling complex, Sin3a-HDAC (B). As a consequence, KLF11 behaves as a tumor suppressor in Barrett's epithelial cells, at least in part, by repression of the cPLA2α-PGE2pathway. EGFR-AKT signaling, which is up-regulated in a subset of patients during carcinogenesis in Barrett's esophagus (C) phosphorylates threonine at position 56 in the R1 domain of KLF11 in the immediate vicinity of its Sin3a interacting domain (D), and reverses the KLF11-dependent repression of the cPLA2α promoter (E). Together, this model outlines mechanistic links, namely KLF11-SIN3a/HDAC-cPLA2α-PGE2 and EGFR/AKT-KLF11 (Thr-56 phosphorylation)-SIN3a/HDAC-cPLA2α-PGE2.
Mechanistic model of KLF11-mediated tumor suppression and its antagonism by an oncogenic pathway
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Publication

Distinct Role of Kruppel-like Factor 11 in the Regulation of Prostaglandin E2 Biosynthesis. (2010) Navtej S. Buttar, et al. J Biol Chem. 2010 Apr 9;285(15):11433-11444. Figure: F7.

Gene mentions


Organism Group Word Match Source NCBI Symbol NCBI ID
Drosophila melanogaster Invertebrates EGFR EGFR ncbigene_symbol Egfr 37455
Drosophila melanogaster Invertebrates PDK1 PDK1 ncbigene_symbol Pdk1 38017
Drosophila melanogaster Invertebrates AKT AKT ncbigene_symbol Akt 41957
Drosophila melanogaster Invertebrates Sin3a SIN3A ncbigene_symbol Sin3A 36382
Drosophila melanogaster Invertebrates HDAC HDAC ncbigene_synonym HDAC4 32278
Drosophila melanogaster Invertebrates HDAC HDAC ncbigene_synonym HDAC6 32461
Drosophila melanogaster Invertebrates HDAC HDAC ncbigene_synonym HDAC1 38565
Drosophila melanogaster Invertebrates HDAC HDAC ncbigene_synonym HDAC3 44446
Drosophila melanogaster Invertebrates Ac AC ncbigene_symbol ac 30981
Homo sapiens Primates EGFR EGFR ncbigene_symbol EGFR 1956
Homo sapiens Primates PDK1 PDK1 ncbigene_symbol PDK1 5163
Homo sapiens Primates PDK1 PDK1 ncbigene_synonym PDPK1 5170
Homo sapiens Primates AKT AKT ncbigene_synonym AKT1 207
Homo sapiens Primates AKT AKT famplex_relations AKT2 208
Homo sapiens Primates AKT AKT famplex_relations AKT3 10000
Homo sapiens Primates Sin3a SIN3A ncbigene_symbol SIN3A 25942
Homo sapiens Primates HDAC HDAC ncbigene_synonym HDAC9 9734
Homo sapiens Primates HDAC HDAC famplex_relations HDAC1 3065
Homo sapiens Primates HDAC HDAC famplex_relations HDAC2 3066
Homo sapiens Primates HDAC HDAC famplex_relations HDAC3 8841
Homo sapiens Primates HDAC HDAC famplex_relations HDAC8 55869
Homo sapiens Primates HDAC HDAC famplex_relations HDAC4 9759
Homo sapiens Primates HDAC HDAC famplex_relations HDAC5 10014
Homo sapiens Primates HDAC HDAC famplex_relations HDAC7 51564
Homo sapiens Primates HDAC HDAC famplex_relations HDAC6 10013
Homo sapiens Primates HDAC HDAC famplex_relations HDAC10 83933
Homo sapiens Primates HDAC HDAC famplex_relations SIRT1 23411
Homo sapiens Primates HDAC HDAC famplex_relations SIRT2 22933
Homo sapiens Primates HDAC HDAC famplex_relations SIRT3 23410
Homo sapiens Primates HDAC HDAC famplex_relations SIRT4 23409
Homo sapiens Primates HDAC HDAC famplex_relations SIRT5 23408
Homo sapiens Primates HDAC HDAC famplex_relations SIRT6 51548
Homo sapiens Primates HDAC HDAC famplex_relations SIRT7 51547
Homo sapiens Primates HDAC HDAC famplex_relations HDAC11 79885
Homo sapiens Primates (KLF11 KLF11 ncbigene_symbol KLF11 8462
Homo sapiens Primates Ac ADCY famplex_relations ADCY1 107
Homo sapiens Primates Ac ADCY famplex_relations ADCY2 108
Homo sapiens Primates Ac ADCY famplex_relations ADCY3 109
Homo sapiens Primates Ac ADCY famplex_relations ADCY4 196883
Homo sapiens Primates Ac ADCY famplex_relations ADCY5 111
Homo sapiens Primates Ac ADCY famplex_relations ADCY6 112
Homo sapiens Primates Ac ADCY famplex_relations ADCY7 113
Homo sapiens Primates Ac ADCY famplex_relations ADCY8 114
Homo sapiens Primates Ac ADCY famplex_relations ADCY9 115
Homo sapiens Primates Ac ADCY famplex_relations ADCY10 55811
Homo sapiens Primates CPLA2 CPLA2 ncbigene_synonym PLA2G4A 5321
Homo sapiens Primates CPLA2 CPLA2 ncbigene_synonym KAT5 10524

Chemical mentions

Word Match MeSH Name ChEBI
PGE2 Dinoprostone mesh:D015232 prostaglandin E2 chebi:15551

Disease mentions

Word Match MeSH Name DOID