Differential expression of full-length and NH2terminally truncated FAM134B isoforms in normal physiology and cancer
Küçük Resim Yok
Tarih
2020
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
American Physiological Society
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Keles 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.
Açıklama
Anahtar Kelimeler
Autophagy, Endoplasmic reticulum, ER-phagy, Gene expression, Gene knockout, Hepatocellular carcinoma, Reticulophagy
Kaynak
American Journal of Physiology - Gastrointestinal and Liver Physiology
WoS Q Değeri
Scopus Q Değeri
Q1
Cilt
319
Sayı
6
