Differential expression of full-length and NH<sub>2</sub> terminally truncated FAM134B isoforms in normal physiology and cancer.


Keles U., Iscan E., Yilmaz H. E., Karakulah G., SUNER KARAKÜLAH A., Bal E., ...Daha Fazla

American journal of physiology. Gastrointestinal and liver physiology, cilt.319, sa.6, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 319 Sayı: 6
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1152/ajpgi.00094.2020
  • Dergi Adı: American journal of physiology. Gastrointestinal and liver physiology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chimica, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: autophagy, endoplasmic reticulum, ER-phagy, gene expression, gene knockout, hepatocellular carcinoma, reticulophagy, GOLGI PROTEIN, MICE, METABOLISM, AUTOPHAGY, CHOLESTEROL, INHIBITION, STARVATION
  • Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Evet

Özet

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 NH2 terminally 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. NH2 terminally 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 NH2 terminally truncated FAM134B or both isoforms were downregulated in liver, lung, and colon cancers. In contrast, upregulation was observed in stomach and chromophobe kidney cancers.