Folliculin-interacting proteins Fnip1 and Fnip2 play critical roles in kidney tumor suppression in cooperation with Flcn

Proceedings of the National Academy of Sciences of the United States of America
Hisashi HasumiLaura S Schmidt

Abstract

Folliculin (FLCN)-interacting proteins 1 and 2 (FNIP1, FNIP2) are homologous binding partners of FLCN, a tumor suppressor for kidney cancer. Recent studies have revealed potential functions for Flcn in kidney; however, kidney-specific functions for Fnip1 and Fnip2 are unknown. Here we demonstrate that Fnip1 and Fnip2 play critical roles in kidney tumor suppression in cooperation with Flcn. We observed no detectable phenotype in Fnip2 knockout mice, whereas Fnip1 deficiency produced phenotypes similar to those seen in Flcn-deficient mice in multiple organs, but not in kidneys. We found that absolute Fnip2 mRNA copy number was low relative to Fnip1 in organs that showed phenotypes under Fnip1 deficiency but was comparable to Fnip1 mRNA copy number in mouse kidney. Strikingly, kidney-targeted Fnip1/Fnip2 double inactivation produced enlarged polycystic kidneys, as was previously reported in Flcn-deficient kidneys. Kidney-specific Flcn inactivation did not further augment kidney size or cystic histology of Fnip1/Fnip2 double-deficient kidneys, suggesting pathways dysregulated in Flcn-deficient kidneys and Fnip1/Fnip2 double-deficient kidneys are convergent. Heterozygous Fnip1/homozygous Fnip2 double-knockout mice developed kidney c...Continue Reading

References

Dec 1, 1977·Archives of Dermatology·A R BirtW J Dubé
Jun 29, 2002·Journal of the American Society of Nephrology : JASN·Xinli ShaoPeter Igarashi
Jun 16, 2005·Journal of the National Cancer Institute·Cathy D VockeW Marston Linehan
Oct 10, 2006·Proceedings of the National Academy of Sciences of the United States of America·Masaya BabaBerton Zbar
Oct 24, 2009·Proceedings of the National Academy of Sciences of the United States of America·Yukiko HasumiW Marston Linehan
Nov 15, 2012·Journal of the National Cancer Institute·Hisashi HasumiW Marston Linehan
May 3, 2013·Nature·Cyriac KandothDouglas A Levine
Jun 25, 2013·Nature·UNKNOWN Cancer Genome Atlas Research Network
Oct 2, 2013·The Journal of Cell Biology·Constance S PetitShawn M Ferguson
Apr 26, 2014·The Journal of Clinical Investigation·Ming YanArnim Pause
Apr 26, 2014·PLoS Genetics·Elite PossikArnim Pause
Jun 9, 2014·Human Molecular Genetics·Yukiko HasumiW Marston Linehan

❮ Previous
Next ❯

Citations

Sep 4, 2015·Nature Reviews. Urology·Laura S Schmidt, W Marston Linehan
Nov 27, 2015·International Journal of Urology : Official Journal of the Japanese Urological Association·Hisashi HasumiMasahiro Yao
Jun 16, 2016·Proceedings of the National Academy of Sciences of the United States of America·Owen M SiggsRichard J Cornall
Aug 16, 2016·Clinics in Chest Medicine·Nishant GuptaRobert M Kotloff
Mar 23, 2017·European Clinical Respiratory Journal·Dea Kejlberg JensenElisabeth Bendstrup
Jan 10, 2018·Frontiers in Neuroscience·Lindsey B SheltonLaura J Blair
Jun 30, 2016·Nature Communications·Mark R WoodfordMehdi Mollapour
Dec 27, 2019·Journal of the European Academy of Dermatology and Venereology : JEADV·L DiluvioA Terrinoni
May 24, 2020·Evolution; International Journal of Organic Evolution·Alexandra K FraikAndrew Storfer
Mar 21, 2020·Frontiers in Cell and Developmental Biology·Natàlia de Martín Garrido, Christopher H S Aylett
Apr 2, 2020·American Journal of Medical Genetics. Part a·Zeynep H Coban-AkdemirSeema R Lalani
Apr 14, 2016·The Journal of Biological Chemistry·Mingming ZhongYu Jiang
Aug 14, 2018·Genes & Genomics·Ki Hwan HongJeong Hwan Moon
Nov 3, 2020·PLoS Genetics·Lene ClausenRasmus Hartmann-Petersen
Feb 21, 2021·The Journal of Biological Chemistry·Xiaojuan WangWei Liu
Nov 11, 2019·Cell·Kuang ShenDavid M Sabatini
Oct 14, 2019·Archives of Biochemistry and Biophysics·Zheng WuLiang Yuan
May 14, 2021·Frontiers in Cell and Developmental Biology·Josué M J Ramirez ReyesArnim Pause
Dec 7, 2019·Biochemical and Biophysical Research Communications·Yasuhiro IsonoHisashi Hasumi

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.