Differential expression of full-length and NH2terminally truncated FAM134B isoforms in normal physiology and cancer

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dc.contributor.authorKeles U.
dc.contributor.authorIscan E.
dc.contributor.authorYilmaz H.E.
dc.contributor.authorKarakülah G.
dc.contributor.authorSuner A.
dc.contributor.authorBal E.
dc.contributor.authorKahyaoglu S.
dc.date.accessioned2021-05-03T20:52:00Z
dc.date.available2021-05-03T20:52:00Z
dc.date.issued2020
dc.description.abstractKeles U, Iscan E, Yilmaz HE, Karakulah G, Suner A, Bal E, Tasdemir N, Cavga AD, Ekin U, Mutlu Z, Kahyaoglu S, Serdar MA, Atabey N, Ozturk M. Differential expression of full-length and NH2terminally truncated FAM134B isoforms in normal physiology and cancer. Am J Physiol Gastrointest Liver Physiol 319: G733-G747, 2020. First published October 14, 2020; doi:10.1152/ ajpgi.00094.2020.-Selective autophagy of the endoplasmic reticulum (ER), namely ER-phagy, is mediated by ER-localized receptors, which are recognized and sequestered by GABARAP/LC3B-decorated phagophores and transferred to lysosomes for degradation. Being one such receptor, FAM134B plays critical roles in cellular processes such as protein quality control and neuronal survival. FAM134B has also been associated with different cancers, although its exact role remains elusive. We report here that the FAM134B gene encodes not one but at least two different protein isoforms: the full-length and the NH2terminally truncated forms. Their relative expression shows extreme variation, both within normal tissues and among cancer types. Expression of full-length FAM134B is restricted to the brain, testis, spleen, and prostate. In contrast, NH2 terminally truncated FAM134B is dominant in the heart, skeletal muscle, kidney, pancreas, and liver. We compared wild-type and knockout mice to study the role of the Fam134b gene in starvation. NH2terminally truncated FAM134B-2 was induced in the liver, skeletal muscle, and heart but not in the pancreas and stomach following starvation. Upon starvation, Fam134b-/-mice differed from wild-type mice by less weight loss and less hyperaminoacidemic and hypocalcemic response but increased levels of serum albumin, total serum proteins, and a-amylase. Interestingly, either NH2terminally truncated FAM134B or both isoforms were downregulated in liver, lung, and colon cancers. In contrast, upregulation was observed in stomach and chromophobe kidney cancers. NEW & NOTEWORTHY We reported tissues expressing FAM134B-2 such as the kidney, muscle, heart, and pancreas, some of which exhibit stimulated expression upon nutrient starvation. We also demonstrated the effect of Fam134b deletion during ad libitum and starvation conditions. Resistance to weight loss and hypocalcemia, accompanied by an increase in serum albumin and a-amylase levels, indicate critical roles of Fam134b in physiology. Furthermore, the differential expression of FAM134B isoforms was shown to be significantly dysregulated in human cancers. © 2020 American Physiological Society. All rights reserved.en_US
dc.description.sponsorshipNational Institutes of Health, NIH National Institute of Mental Health, NIMH National Institute on Drug Abuse, NIDA National Heart, Lung, and Blood Institute, NHLBI National Human Genome Research Institute, NHGRI National Cancer Institute, NCI National Institute of Neurological Disorders and Stroke, NINDS Dokuz Eylül Üniversitesi: KB.SAG.047en_US
dc.description.sponsorshipThis study is supported by Dokuz Eylul University, Department of Scientific Research Projects (with the Project code 2014.KB.SAG.047), and Izmir Biomedicine and Genome Center’s (IBG) institutional funds. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health and by the National Cancer Institute, National Human Genome Research Institute, National Heart, Lung, and Blood Institute, National Institute on Drug Abuse, National Institute of Mental Health, and National Institute of Neurological Disorders and Stroke. The data used for the analyses described in this article were obtained from the GTEx Portal on 11/14/2018 and/or dbGaP Accession No. phs000424.v3.p1.en_US
dc.description.sponsorshipThis study is supported by Dokuz Eylul University, Department of Scientific Research Projects (with the Project code 2014.KB.SAG.047), and Izmir Biomedicine and Genome Center's (IBG) institutional funds. The Genotype- Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health and by the National Cancer Institute, National Human Genome Research Institute, National Heart, Lung, and Blood Institute, National Institute on Drug Abuse, National Institute of Mental Health, and National Institute of Neurological Disorders and Stroke. The data used for the analyses described in this article were obtained from the GTEx Portal on 11/14/2018 and/or dbGaP Accession No. phs000424.v3.p1. We thank the Izmir Biomedicine and Genome Center-Vivarium Rodent Facility and the optical imaging core facility for great support in the experimental procedures. We are also deeply grateful to Deniz Donmez for efforts in improving the manuscript's language. We also thank Christian Hu7die;bner for kind donation of Fam134b-/-animals.en_US
dc.identifier.doi10.1152/AJPGI.00094.2020en_US
dc.identifier.endpageG747en_US
dc.identifier.issn0193-1857
dc.identifier.issue6en_US
dc.identifier.pmid33052704en_US
dc.identifier.scopus2-s2.0-85098471966en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpageG733en_US
dc.identifier.urihttps://doi.org/10.1152/AJPGI.00094.2020
dc.identifier.urihttps://hdl.handle.net/11454/71005
dc.identifier.volume319en_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherAmerican Physiological Societyen_US
dc.relation.ispartofAmerican Journal of Physiology - Gastrointestinal and Liver Physiologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectAutophagyen_US
dc.subjectEndoplasmic reticulumen_US
dc.subjectER-phagyen_US
dc.subjectGene expressionen_US
dc.subjectGene knockouten_US
dc.subjectHepatocellular carcinomaen_US
dc.subjectReticulophagyen_US
dc.titleDifferential expression of full-length and NH2terminally truncated FAM134B isoforms in normal physiology and canceren_US
dc.typeArticleen_US

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