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Sterile α-motif domain requirement for cellular signaling and survival

Hundreds of sterile α-motif (SAM) domains have predicted structural similarities and are reported to bind proteins, lipids, or RNAs. However, the majority of these domains have not been analyzed functionally. Previously, we demonstrated that a SAM domain-containing protein, SAMD14, promotes SCF/prot...

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Autores principales: Ray, Suhita, Chee, Linda, Matson, Daniel R., Palermo, Nick Y., Bresnick, Emery H., Hewitt, Kyle J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242717/
https://www.ncbi.nlm.nih.gov/pubmed/32241909
http://dx.doi.org/10.1074/jbc.RA119.011895
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author Ray, Suhita
Chee, Linda
Matson, Daniel R.
Palermo, Nick Y.
Bresnick, Emery H.
Hewitt, Kyle J.
author_facet Ray, Suhita
Chee, Linda
Matson, Daniel R.
Palermo, Nick Y.
Bresnick, Emery H.
Hewitt, Kyle J.
author_sort Ray, Suhita
collection PubMed
description Hundreds of sterile α-motif (SAM) domains have predicted structural similarities and are reported to bind proteins, lipids, or RNAs. However, the majority of these domains have not been analyzed functionally. Previously, we demonstrated that a SAM domain-containing protein, SAMD14, promotes SCF/proto-oncogene c-Kit (c-Kit) signaling, erythroid progenitor function, and erythrocyte regeneration. Deletion of a Samd14 enhancer (Samd14–Enh), occupied by GATA2 and SCL/TAL1 transcription factors, reduces SAMD14 expression in bone marrow and spleen and is lethal in a hemolytic anemia mouse model. To rigorously establish whether Samd14–Enh deletion reduces anemia-dependent c-Kit signaling by lowering SAMD14 levels, we developed a genetic rescue assay in murine Samd14–Enh(−/−) primary erythroid precursor cells. SAMD14 expression at endogenous levels rescued c-Kit signaling. The conserved SAM domain was required for SAMD14 to increase colony-forming activity, c-Kit signaling, and progenitor survival. To elucidate the molecular determinants of SAM domain function in SAMD14, we substituted its SAM domain with distinct SAM domains predicted to be structurally similar. The chimeras were less effective than SAMD14 itself in rescuing signaling, survival, and colony-forming activities. Thus, the SAMD14 SAM domain has attributes that are distinct from other SAM domains and underlie SAMD14 function as a regulator of cellular signaling and erythrocyte regeneration.
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spelling pubmed-72427172020-06-05 Sterile α-motif domain requirement for cellular signaling and survival Ray, Suhita Chee, Linda Matson, Daniel R. Palermo, Nick Y. Bresnick, Emery H. Hewitt, Kyle J. J Biol Chem Cell Biology Hundreds of sterile α-motif (SAM) domains have predicted structural similarities and are reported to bind proteins, lipids, or RNAs. However, the majority of these domains have not been analyzed functionally. Previously, we demonstrated that a SAM domain-containing protein, SAMD14, promotes SCF/proto-oncogene c-Kit (c-Kit) signaling, erythroid progenitor function, and erythrocyte regeneration. Deletion of a Samd14 enhancer (Samd14–Enh), occupied by GATA2 and SCL/TAL1 transcription factors, reduces SAMD14 expression in bone marrow and spleen and is lethal in a hemolytic anemia mouse model. To rigorously establish whether Samd14–Enh deletion reduces anemia-dependent c-Kit signaling by lowering SAMD14 levels, we developed a genetic rescue assay in murine Samd14–Enh(−/−) primary erythroid precursor cells. SAMD14 expression at endogenous levels rescued c-Kit signaling. The conserved SAM domain was required for SAMD14 to increase colony-forming activity, c-Kit signaling, and progenitor survival. To elucidate the molecular determinants of SAM domain function in SAMD14, we substituted its SAM domain with distinct SAM domains predicted to be structurally similar. The chimeras were less effective than SAMD14 itself in rescuing signaling, survival, and colony-forming activities. Thus, the SAMD14 SAM domain has attributes that are distinct from other SAM domains and underlie SAMD14 function as a regulator of cellular signaling and erythrocyte regeneration. American Society for Biochemistry and Molecular Biology 2020-05-15 2020-04-02 /pmc/articles/PMC7242717/ /pubmed/32241909 http://dx.doi.org/10.1074/jbc.RA119.011895 Text en © 2020 Ray et al. Author's Choice—Final version open access under the terms of the Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0) .
spellingShingle Cell Biology
Ray, Suhita
Chee, Linda
Matson, Daniel R.
Palermo, Nick Y.
Bresnick, Emery H.
Hewitt, Kyle J.
Sterile α-motif domain requirement for cellular signaling and survival
title Sterile α-motif domain requirement for cellular signaling and survival
title_full Sterile α-motif domain requirement for cellular signaling and survival
title_fullStr Sterile α-motif domain requirement for cellular signaling and survival
title_full_unstemmed Sterile α-motif domain requirement for cellular signaling and survival
title_short Sterile α-motif domain requirement for cellular signaling and survival
title_sort sterile α-motif domain requirement for cellular signaling and survival
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242717/
https://www.ncbi.nlm.nih.gov/pubmed/32241909
http://dx.doi.org/10.1074/jbc.RA119.011895
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