CDK1 interacts with RARγ and plays an important role in treatment response of acute myeloid leukemia.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3627814
- author
- 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
- organization
- publishing date
- 2013
- 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
- pmid:23518499
- 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
- 2016-04-01 10:10:12
- date last changed
- 2023-01-02 01:51:45
@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}}, doi = {{10.4161/cc.24313}}, volume = {{12}}, year = {{2013}}, }