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CDK1 interacts with RARγ and plays an important role in treatment response of acute myeloid leukemia.

Hedblom, Andreas LU ; Laursen, Kristian B; Miftakhova, Regina LU ; Sarwar, Martuza LU ; Anagnostaki, Lola; Bredberg, Anders LU ; Mongan, Nigel LU ; Gudas, Lorraine J and Persson, Jenny L LU (2013) In Cell Cycle 12(8). p.1251-1266
Abstract
Alterations in cell cycle pathways and retinoic acid signaling are implicated in leukemogenesis. However, little is known about the roles of cyclin-dependent kinases (CDKs) in treatment response of leukemia. In this study, we observed that CDK1 expression was significantly higher in bone marrow from 42 patients with acute myeloid leukemia (AML) at recurrence than that at first diagnosis (p = 0.04). AML patients had higher level of nuclear CDK1 in their leukemic blasts tended to have poorer clinical outcome compared with those with lower levels. We showed that CDK1 function is required for all-trans retinoic acid (ATRA) to achieve the optimal effect in U-937 human leukemic cells. CDK1 modulates the levels of P27 (kip) and AKT... (More)
Alterations in cell cycle pathways and retinoic acid signaling are implicated in leukemogenesis. However, little is known about the roles of cyclin-dependent kinases (CDKs) in treatment response of leukemia. In this study, we observed that CDK1 expression was significantly higher in bone marrow from 42 patients with acute myeloid leukemia (AML) at recurrence than that at first diagnosis (p = 0.04). AML patients had higher level of nuclear CDK1 in their leukemic blasts tended to have poorer clinical outcome compared with those with lower levels. We showed that CDK1 function is required for all-trans retinoic acid (ATRA) to achieve the optimal effect in U-937 human leukemic cells. CDK1 modulates the levels of P27 (kip) and AKT phosphorylation in response to ATRA treatment. Further, we show, for the first time, that RARγ in concert with ATRA regulates protein levels of CDK1 and its subcellular localization. The regulation of the subcellular content of CDK1 and RARγ by ATRA is an important process for achieving an effective response in treatment of leukemia. RARγ and CDK1 form a reciprocal regulatory circuit in the nucleus and influence the function and protein stability of each other and the level of P27 (kip) protein. In addition, expression of wee1 kinase and Cdc25A/C phosphatases also coincide with CDK1 expression and its subcellular localization in response to ATRA treatment. Our study reveals a novel mechanism by which CDK1 and RARγ coordinate with ATRA to influence cell cycle progression and cellular differentiation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cell Cycle
volume
12
issue
8
pages
1251 - 1266
publisher
Landes Bioscience
external identifiers
  • wos:000318067700017
  • pmid:23518499
  • scopus:84876244657
ISSN
1551-4005
DOI
10.4161/cc.24313
language
English
LU publication?
yes
id
2f848f12-5b44-49ba-99d8-03cf7d2d83b0 (old id 3627814)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23518499?dopt=Abstract
date added to LUP
2013-04-07 15:59:32
date last changed
2019-04-23 01:11:57
@article{2f848f12-5b44-49ba-99d8-03cf7d2d83b0,
  abstract     = {Alterations in cell cycle pathways and retinoic acid signaling are implicated in leukemogenesis. However, little is known about the roles of cyclin-dependent kinases (CDKs) in treatment response of leukemia. In this study, we observed that CDK1 expression was significantly higher in bone marrow from 42 patients with acute myeloid leukemia (AML) at recurrence than that at first diagnosis (p = 0.04). AML patients had higher level of nuclear CDK1 in their leukemic blasts tended to have poorer clinical outcome compared with those with lower levels. We showed that CDK1 function is required for all-trans retinoic acid (ATRA) to achieve the optimal effect in U-937 human leukemic cells. CDK1 modulates the levels of P27 (kip) and AKT phosphorylation in response to ATRA treatment. Further, we show, for the first time, that RARγ in concert with ATRA regulates protein levels of CDK1 and its subcellular localization. The regulation of the subcellular content of CDK1 and RARγ by ATRA is an important process for achieving an effective response in treatment of leukemia. RARγ and CDK1 form a reciprocal regulatory circuit in the nucleus and influence the function and protein stability of each other and the level of P27 (kip) protein. In addition, expression of wee1 kinase and Cdc25A/C phosphatases also coincide with CDK1 expression and its subcellular localization in response to ATRA treatment. Our study reveals a novel mechanism by which CDK1 and RARγ coordinate with ATRA to influence cell cycle progression and cellular differentiation.},
  author       = {Hedblom, Andreas and Laursen, Kristian B and Miftakhova, Regina and Sarwar, Martuza and Anagnostaki, Lola and Bredberg, Anders and Mongan, Nigel and Gudas, Lorraine J and Persson, Jenny L},
  issn         = {1551-4005},
  language     = {eng},
  number       = {8},
  pages        = {1251--1266},
  publisher    = {Landes Bioscience},
  series       = {Cell Cycle},
  title        = {CDK1 interacts with RARγ and plays an important role in treatment response of acute myeloid leukemia.},
  url          = {http://dx.doi.org/10.4161/cc.24313},
  volume       = {12},
  year         = {2013},
}