PMID- 21163929
OWN - NLM
STAT- MEDLINE
DCOM- 20110331
LR  - 20211020
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 117
IP  - 7
DP  - 2011 Feb 17
TI  - Noxa mediates p18INK4c cell-cycle control of homeostasis in B cells and plasma 
      cell precursors.
PG  - 2179-88
LID - 10.1182/blood-2010-06-288027 [doi]
AB  - Inhibition of Cdk4/Cdk6 by p18(INK4c) (p18) is pivotal for generation of 
      noncycling immunoglobulin (Ig)-secreting plasma cells (PCs). In the absence of 
      p18, CD138(+) plasmacytoid cells continue to cycle and turnover rapidly, 
      suggesting that p18 controls PC homeostasis. We now show that p18 selectively 
      acts in a rare population of rapidly cycling CD138(hi)/B220(hi) intermediate PCs 
      (iPCs). While retaining certain B-cell signatures, iPCs are poised to 
      differentiate to end-stage PCs although the majority undergo apoptosis. p18 is 
      dispensable for the development of the PC transcriptional circuitry, and Blimp-1 
      and Bcl-6 are expressed fully and mutually exclusively in individual iPCs. 
      However, a minor proportion of iPCs express both, and they are preferentially 
      protected by p18 or Bcl-xL overexpression, consistent with expansion of the iPC 
      pool by Bcl-xL overexpression, or loss of proapoptotic Bim or Noxa. Expression of 
      Noxa is induced during B-cell activation, peaks in iPCs, and selectively 
      repressed by p18. It is required to promote apoptosis of cycling B cells, 
      especially in the absence of p18. These findings define the first physiologic 
      function for Noxa and suggest that by repressing Noxa, induction of G(1) arrest by 
      p18 bypasses a homeostatic cell-cycle checkpoint in iPCs for PC differentiation.
FAU - Bretz, Jamieson
AU  - Bretz J
AD  - Department of Pathology, Weill Medical College of Cornell University, New York, 
      NY, USA.
FAU - Garcia, Josefina
AU  - Garcia J
FAU - Huang, Xiangao
AU  - Huang X
FAU - Kang, Lin
AU  - Kang L
FAU - Zhang, Yang
AU  - Zhang Y
FAU - Toellner, Kai-Michael
AU  - Toellner KM
FAU - Chen-Kiang, Selina
AU  - Chen-Kiang S
LA  - eng
GR  - R01 AR049436/AR/NIAMS NIH HHS/United States
GR  - R01 CA120531/CA/NCI NIH HHS/United States
GR  - T32-CA120531/CA/NCI NIH HHS/United States
GR  - T32-AR 49436/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20101216
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Bcl2l1 protein, mouse)
RN  - 0 (Cdkn2c protein, mouse)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p18)
RN  - 0 (Immunoglobulin G)
RN  - 0 (PMAIP1 protein, human)
RN  - 0 (Pmaip1 protein, mouse)
RN  - 0 (Prdm1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Proto-Oncogene Proteins c-bcl-6)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Sdc1 protein, mouse)
RN  - 0 (Syndecan-1)
RN  - 0 (Transcription Factors)
RN  - 0 (bcl-X Protein)
RN  - EC 2.1.1.- (Positive Regulatory Domain I-Binding Factor 1)
RN  - EC 3.1.3.48 (Leukocyte Common Antigens)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics/physiology
MH  - B-Lymphocytes/*cytology/*physiology
MH  - Cell Cycle/genetics/physiology
MH  - Cell Differentiation/genetics/physiology
MH  - Cyclin-Dependent Kinase Inhibitor p18/deficiency/genetics/*physiology
MH  - HEK293 Cells
MH  - Hematopoietic Stem Cells/cytology/physiology
MH  - Homeostasis/genetics/physiology
MH  - Humans
MH  - Immunoglobulin G/biosynthesis
MH  - Leukocyte Common Antigens/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Models, Biological
MH  - Plasma Cells/*cytology/*physiology
MH  - Positive Regulatory Domain I-Binding Factor 1
MH  - Proto-Oncogene Proteins c-bcl-2/antagonists & 
      inhibitors/deficiency/genetics/*physiology
MH  - Proto-Oncogene Proteins c-bcl-6/genetics/physiology
MH  - RNA, Small Interfering/genetics
MH  - Syndecan-1/metabolism
MH  - Transcription Factors/genetics/physiology
MH  - bcl-X Protein/genetics/physiology
PMC - PMC3062327
EDAT- 2010/12/18 06:00
MHDA- 2011/04/01 06:00
PMCR- 2012/02/17
CRDT- 2010/12/18 06:00
PHST- 2010/12/18 06:00 [entrez]
PHST- 2010/12/18 06:00 [pubmed]
PHST- 2011/04/01 06:00 [medline]
PHST- 2012/02/17 00:00 [pmc-release]
AID - S0006-4971(20)55098-2 [pii]
AID - 2010/288027 [pii]
AID - 10.1182/blood-2010-06-288027 [doi]
PST - ppublish
SO  - Blood. 2011 Feb 17;117(7):2179-88. doi: 10.1182/blood-2010-06-288027. Epub 2010 
      Dec 16.