Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Differential expression of full-length and NH2 terminally truncated FAM134B isoforms in normal physiology and cancer

Keles, Umur LU ; Iscan, Evin ; Yilmaz, Huriye Erbak ; Karakülah, Gökhan ; Suner, Aslı ; Bal, Erhan ; Tasdemir, Nilgun ; Cavga, Ayse Derya ; Ekin, Umut and Mutlu, Zeynep , et al. (2020) In American Journal of Physiology: Gastrointestinal and Liver Physiology 319(6). p.733-747
Abstract

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... (More)

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 α-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.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 α-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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; and (Less)
publishing date
type
Contribution to journal
publication status
published
keywords
Adult, Animals, Autophagy, Cell Line, Tumor, Endoplasmic Reticulum/metabolism, Female, Gene Expression Regulation, Neoplastic/genetics, Humans, Intracellular Signaling Peptides and Proteins/biosynthesis, Isomerism, Male, Membrane Proteins/biosynthesis, Mice, Mice, Knockout, Neoplasms/genetics, Starvation/metabolism, Tissue Distribution
in
American Journal of Physiology: Gastrointestinal and Liver Physiology
volume
319
issue
6
pages
733 - 747
publisher
American Physiological Society
external identifiers
  • scopus:85098471966
  • pmid:33052704
ISSN
1522-1547
DOI
10.1152/ajpgi.00094.2020
language
English
LU publication?
no
id
1c4f01d8-104c-4193-bd8d-ebe3009656c9
date added to LUP
2022-12-28 10:10:02
date last changed
2024-04-04 14:54:10
@article{1c4f01d8-104c-4193-bd8d-ebe3009656c9,
  abstract     = {{<p>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 α-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.NEW &amp; 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 α-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.</p>}},
  author       = {{Keles, Umur and Iscan, Evin and Yilmaz, Huriye Erbak and Karakülah, Gökhan and Suner, Aslı and Bal, Erhan and Tasdemir, Nilgun and Cavga, Ayse Derya and Ekin, Umut and Mutlu, Zeynep and Kahyaoglu, Sila and Serdar, Muhittin A and Atabey, Nese and Ozturk, Mehmet}},
  issn         = {{1522-1547}},
  keywords     = {{Adult; Animals; Autophagy; Cell Line, Tumor; Endoplasmic Reticulum/metabolism; Female; Gene Expression Regulation, Neoplastic/genetics; Humans; Intracellular Signaling Peptides and Proteins/biosynthesis; Isomerism; Male; Membrane Proteins/biosynthesis; Mice; Mice, Knockout; Neoplasms/genetics; Starvation/metabolism; Tissue Distribution}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{6}},
  pages        = {{733--747}},
  publisher    = {{American Physiological Society}},
  series       = {{American Journal of Physiology: Gastrointestinal and Liver Physiology}},
  title        = {{Differential expression of full-length and NH2 terminally truncated FAM134B isoforms in normal physiology and cancer}},
  url          = {{http://dx.doi.org/10.1152/ajpgi.00094.2020}},
  doi          = {{10.1152/ajpgi.00094.2020}},
  volume       = {{319}},
  year         = {{2020}},
}