Official Full Name
platelet-activating factor acetylhydrolase 1b, catalytic subunit 2 (30kDa)
Platelet-activating factor acetylhydrolase (PAFAH) inactivates platelet-activating factor (PAF) into acetate and;LYSO-PAF. This gene encodes the beta subunit of PAFAH, the other subunits are alpha and gamma. Multiple alternatively;spliced transcript variants that encode different protein isoforms have been described for this gene.
PAFAH1B2; platelet-activating factor acetylhydrolase 1b, catalytic subunit 2 (30kDa); platelet-activating factor acetylhydrolase IB subunit beta; PAF acetylhydrolase 30 kDa subunit; PAF AH 30 kDa subunit; PAF AH beta subunit; PAF AH subunit beta; PAFAH 30 kDa subunit; PAFAH beta subunit; PAFAH subunit beta; PAFAH1B2 protein; PAFAHB; Platelet activating factor acetylhydrolase IB beta subunit; Platelet activating factor acetylhydrolase IB subunit beta; Platelet activating factor acetylhydrolase isoform Ib beta subunit; PAF-AH subunit beta; PAF-AH 30 kDa subunit; platelet-activating factor acetylhydrolase, isoform Ib, subunit 2 (30kDa); platelet-activating factor acetylhydrolase, isoform Ib, beta subunit 30kDa; platelet-activating factor acetylhydrolase, isoform Ib, beta subunit (30kD); platelet activating factor acetylhydrolase, isoform Ib, beta subunit 30kDa , platelet activating factor acetylhydrolase, isoform Ib, subunit 2 (30kDa); PAF AH1b alpha 2 subunit; PAF-AH1b alpha 2 subunit; intracellular platelet-activating factor acetylhydrolase alpha 2 subunit; platelet-; platelet-activating factor acetylhydrolase 1b, catalytic subunit 2; si:ch211-139a5.3
PAFAH1B2 and Cancer
Platelet-activating factor acetylhydrolase IB subunit beta (PAFAH1B2) is the catalytic subunit of platelet-activating factor acetylhydrolase (PAF-AH), a calculated molecular mass of 30 kDa. PAFAH1B2 has been shown to be overexpressed in some types of tumors such as breast cancer, lung cancer, and lymphoma. According to previous studies, platelet-activating factor acetylhydrolase IB subunit beta plays an important role in inflammation and anaphylaxis. In the recent study, PAFAH1B2 is overexpressed in pancreatic ductal adenocarcinoma (PDAC), resulting in epithelial emesenchymal transition (EMT), migration and invasion in vitro and metastasis in vivo, which is correlated inversely with patient survival. PAFAH1B2 overexpression in patients with PDAC is associated with the HIF1a. Based on these results, inhibition of PAFAH1B2 expression may be a new therapeutic strategy for the treatment of metastatic PDAC.
PAFAH1B2 can hydrolyze the lipid substances known as platelet activating factor (PAF), and RNAi-mediated knockdown of PAFAH1B2 does not alter PAF levels or PAF hydrolytic activity, indicating that the enzyme may possess alternate endogenous substrates. Rebecca A. Kohnz et al. recently discovered the oncogenic regulatory mechanisms for several cancer-relevant serine hydrolases. In their study, they found that pharmacological blockade of this enzyme impairs the pathogenicity across multiple different types of cancer including breast, ovarian, melanoma, and prostate cancer, while the pharmacological blockade of PAFAH1B2 causes unique changes in lipid metabolism, including heightened levels of tumor-suppressing lipids. They also observed that PAFAH1B2 is also highly expressed in multiple other human cancer cell lines (C8161, MUM2C melanoma, SKOV3 ovarian and MCF7 breast cancer cells) and inactivation of PAFAH1B2 leads to far wider alterations in lipid metabolism including increases in several tumor-suppressing lipids. These evidences suggest that PAFAH1B2 is important in maintaining cancer pathogenicity across a wide spectrum of cancer types.
Figure 1. PAFAH1B2 protein (predicted Homo sapiens).
Gang Zhou, Gopal K. Marathe, Belinda Willard, and Thomas M. McIntyre. (2011) 'Intracellular Erythrocyte Platelet-activating Factor Acetylhydrolase I Inactivates Aspirin in Blood', BIOLOGICAL CHEMISTRY，286(40).
Rebecca A. Kohnz, Melinda M. Mulvihill, Jae Won Chang, Ku-Lung Hsu, Antonio Sorrentino, Benjamin F. Cravatt, Sourav Bandyopadhyay, Andrei Goga and Daniel K. Nomura. (2015) 'Activity-Based Protein Profiling of Oncogene-Driven Changes in Metabolism Reveals Broad Dysregulation of PAFAH1B2 and 1B3 in Cancer', ACS Chem. Biol, 10:1624-1630.
Can Ma a, Yan Guo b, Yan Zhang a, Aixia Duo a, Yitao Jia a, Ci Liu a and Binghui Li. (2018) ' PAFAH1B2 is a HIF1a target gene and promotes metastasis in pancreatic cancer', Biochemical and Biophysical Research Communications, 501:654-660.