Cul4A is required for hematopoietic stem-cell engraftment and self-renewal

Binghui Li, Nan Jia, David L. Waning, Feng Chun Yang, Laura S. Haneline, Kristin T. Chun

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Several hematopoietic stem-cell (HSC) regulators are controlled by ubiquitin-mediated proteolysis, so the ubiquitin pathway might modulate HSC function. However, this hypothesis has not been formally tested. Cul4A encodes a core subunit of one ubiquitin ligase. Whereas Cul4A-deficient embryos die in utero, Cul4A-haploinsufficient mice are viable but exhibit abnormal hematopoiesis (fewer erythroid and primitive myeloid progenitors). Given these data, we examined whether Cul4A+/- HSCs might also be impaired. Using bone marrow transplantation assays, we determined that Cul4A+/- HSCs exhibit defects in engraftment and self-renewal capacity. These studies are the first to demonstrate that ubiquitin-mediated protein degradation is important for HSC function. Further, they indicate that a Cul4A ubiquitin ligase targets for degradation one or multiple HSC regulators.

Original languageEnglish (US)
Pages (from-to)2704-2707
Number of pages4
JournalBlood
Volume110
Issue number7
DOIs
StatePublished - Oct 1 2007

Fingerprint

Hematopoietic Stem Cells
Ubiquitin
Stem cells
Ligases
Proteolysis
Degradation
Hematopoiesis
Bone Marrow Transplantation
Assays
Bone
Embryonic Structures
Cell Self Renewal
Defects
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Li, B., Jia, N., Waning, D. L., Yang, F. C., Haneline, L. S., & Chun, K. T. (2007). Cul4A is required for hematopoietic stem-cell engraftment and self-renewal. Blood, 110(7), 2704-2707. https://doi.org/10.1182/blood-2006-12-064154
Li, Binghui ; Jia, Nan ; Waning, David L. ; Yang, Feng Chun ; Haneline, Laura S. ; Chun, Kristin T. / Cul4A is required for hematopoietic stem-cell engraftment and self-renewal. In: Blood. 2007 ; Vol. 110, No. 7. pp. 2704-2707.
@article{4c6e494800e04c229743e2e15fd40167,
title = "Cul4A is required for hematopoietic stem-cell engraftment and self-renewal",
abstract = "Several hematopoietic stem-cell (HSC) regulators are controlled by ubiquitin-mediated proteolysis, so the ubiquitin pathway might modulate HSC function. However, this hypothesis has not been formally tested. Cul4A encodes a core subunit of one ubiquitin ligase. Whereas Cul4A-deficient embryos die in utero, Cul4A-haploinsufficient mice are viable but exhibit abnormal hematopoiesis (fewer erythroid and primitive myeloid progenitors). Given these data, we examined whether Cul4A+/- HSCs might also be impaired. Using bone marrow transplantation assays, we determined that Cul4A+/- HSCs exhibit defects in engraftment and self-renewal capacity. These studies are the first to demonstrate that ubiquitin-mediated protein degradation is important for HSC function. Further, they indicate that a Cul4A ubiquitin ligase targets for degradation one or multiple HSC regulators.",
author = "Binghui Li and Nan Jia and Waning, {David L.} and Yang, {Feng Chun} and Haneline, {Laura S.} and Chun, {Kristin T.}",
year = "2007",
month = "10",
day = "1",
doi = "10.1182/blood-2006-12-064154",
language = "English (US)",
volume = "110",
pages = "2704--2707",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "7",

}

Li, B, Jia, N, Waning, DL, Yang, FC, Haneline, LS & Chun, KT 2007, 'Cul4A is required for hematopoietic stem-cell engraftment and self-renewal', Blood, vol. 110, no. 7, pp. 2704-2707. https://doi.org/10.1182/blood-2006-12-064154

Cul4A is required for hematopoietic stem-cell engraftment and self-renewal. / Li, Binghui; Jia, Nan; Waning, David L.; Yang, Feng Chun; Haneline, Laura S.; Chun, Kristin T.

In: Blood, Vol. 110, No. 7, 01.10.2007, p. 2704-2707.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cul4A is required for hematopoietic stem-cell engraftment and self-renewal

AU - Li, Binghui

AU - Jia, Nan

AU - Waning, David L.

AU - Yang, Feng Chun

AU - Haneline, Laura S.

AU - Chun, Kristin T.

PY - 2007/10/1

Y1 - 2007/10/1

N2 - Several hematopoietic stem-cell (HSC) regulators are controlled by ubiquitin-mediated proteolysis, so the ubiquitin pathway might modulate HSC function. However, this hypothesis has not been formally tested. Cul4A encodes a core subunit of one ubiquitin ligase. Whereas Cul4A-deficient embryos die in utero, Cul4A-haploinsufficient mice are viable but exhibit abnormal hematopoiesis (fewer erythroid and primitive myeloid progenitors). Given these data, we examined whether Cul4A+/- HSCs might also be impaired. Using bone marrow transplantation assays, we determined that Cul4A+/- HSCs exhibit defects in engraftment and self-renewal capacity. These studies are the first to demonstrate that ubiquitin-mediated protein degradation is important for HSC function. Further, they indicate that a Cul4A ubiquitin ligase targets for degradation one or multiple HSC regulators.

AB - Several hematopoietic stem-cell (HSC) regulators are controlled by ubiquitin-mediated proteolysis, so the ubiquitin pathway might modulate HSC function. However, this hypothesis has not been formally tested. Cul4A encodes a core subunit of one ubiquitin ligase. Whereas Cul4A-deficient embryos die in utero, Cul4A-haploinsufficient mice are viable but exhibit abnormal hematopoiesis (fewer erythroid and primitive myeloid progenitors). Given these data, we examined whether Cul4A+/- HSCs might also be impaired. Using bone marrow transplantation assays, we determined that Cul4A+/- HSCs exhibit defects in engraftment and self-renewal capacity. These studies are the first to demonstrate that ubiquitin-mediated protein degradation is important for HSC function. Further, they indicate that a Cul4A ubiquitin ligase targets for degradation one or multiple HSC regulators.

UR - http://www.scopus.com/inward/record.url?scp=34948910184&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34948910184&partnerID=8YFLogxK

U2 - 10.1182/blood-2006-12-064154

DO - 10.1182/blood-2006-12-064154

M3 - Article

C2 - 17616641

AN - SCOPUS:34948910184

VL - 110

SP - 2704

EP - 2707

JO - Blood

JF - Blood

SN - 0006-4971

IS - 7

ER -