The HAPSTR2 retrogene buffers stress signaling and resilience in mammals.

Animals DNA Damage / genetics Mammals / genetics Signal Transduction / genetics Stress, Physiological / genetics Ubiquitin-Protein Ligases / metabolism

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
11 01 2023
Historique:
received: 10 06 2022
accepted: 20 12 2022
entrez: 11 1 2023
pubmed: 12 1 2023
medline: 14 1 2023
Statut: epublish

Résumé

We recently identified HAPSTR1 (C16orf72) as a key component in a novel pathway which regulates the cellular response to molecular stressors, such as DNA damage, nutrient scarcity, and protein misfolding. Here, we identify a functional paralog to HAPSTR1: HAPSTR2. HAPSTR2 formed early in mammalian evolution, via genomic integration of a reverse transcribed HAPSTR1 transcript, and has since been preserved under purifying selection. HAPSTR2, expressed primarily in neural and germline tissues and a subset of cancers, retains established biochemical features of HAPSTR1 to achieve two functions. In normal physiology, HAPSTR2 directly interacts with HAPSTR1, markedly augmenting HAPSTR1 protein stability in a manner independent from HAPSTR1's canonical E3 ligase, HUWE1. Alternatively, in the context of HAPSTR1 loss, HAPSTR2 expression is sufficient to buffer stress signaling and resilience. Thus, we discover a mammalian retrogene which safeguards fitness.

Identifiants

DOI: 10.1038/s41467-022-35697-1 PMID: 36631436 PMC: PMC9834230
pubmed: 36631436
doi: 10.1038/s41467-022-35697-1
pii: 10.1038/s41467-022-35697-1
pmc: PMC9834230
doi:

Substances chimiques

HAPSTR1 protein, human 0
Ubiquitin-Protein Ligases EC 2.3.2.27
HAPSTR2 protein, human 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

152

Subventions

Organisme : NCI NIH HHS
ID : F30 CA264513
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM108569
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA060553
Pays : United States
Organisme : HSRD VA
ID : PPO 16-135
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM133658
Pays : United States
Organisme : NCI NIH HHS
ID : R00 CA175293
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM144617
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM137836
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008152
Pays : United States
Organisme : NIH HHS
ID : S10 OD025194
Pays : United States

Informations de copyright

© 2023. The Author(s).

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Auteurs

David R Amici (DR)

Dept. of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, 60610, USA.
Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, 60610, USA.
Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, 60610, USA.
ORCID: 0000-0003-3318-964X

Harun Cingoz (H)

Dept. of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, 60610, USA.
Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, 60610, USA.
Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, 60610, USA.
ORCID: 0000-0002-3814-585X

Milad J Alasady (MJ)

Dept. of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, 60610, USA.
Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, 60610, USA.
Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, 60610, USA.

Sammy Alhayek (S)

Dept. of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, 60610, USA.
Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, 60610, USA.
Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, 60610, USA.
ORCID: 0000-0002-2351-4894

Claire M Phoumyvong (CM)

Dept. of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, 60610, USA.
Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, 60610, USA.
Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, 60610, USA.

Nidhi Sahni (N)

Department of Epigenetics and Molecular Carcinogenesis, and Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Quantitative and Computational Biosciences Program, Baylor College of Medicine, Houston, TX, 77030, USA.
ORCID: 0000-0002-9155-5882

S Stephen Yi (SS)

Livestrong Cancer Institutes, Department of Oncology, and Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, 78712, USA.
Interdisciplinary Life Sciences Graduate Programs (ILSGP), and Oden Institute for Computational Engineering and Sciences (ICES), The University of Texas at Austin, Austin, TX, 78712, USA.
ORCID: 0000-0003-0047-8103

Marc L Mendillo (ML)

Dept. of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, 60610, USA. mendillo@northwestern.edu.
Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, 60610, USA. mendillo@northwestern.edu.
Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, 60610, USA. mendillo@northwestern.edu.
ORCID: 0000-0001-8128-0128

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › The HAPSTR2 retrogene buffers stress signaling...
questionsmedicales.fr › Phénomènes génétiques › Altération de l'ADN › The HAPSTR2 retrogene buffers stress signaling...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › The HAPSTR2 retrogene buffers stress signaling...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › The HAPSTR2 retrogene buffers stress signaling...
questionsmedicales.fr › Phénomènes physiologiques › Stress physiologique › The HAPSTR2 retrogene buffers stress signaling...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Ligases › Ubiquitin-protein ligase complexes › Ubiquitin-protein ligases › The HAPSTR2 retrogene buffers stress signaling...