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Differential splice isoforms of mouse CDK2 play functionally redundant roles during mitotic and meiotic division

Palmer, Nathan ; Kalem-Yapar, Nisan Ece LU ; Hultén, Hanna LU ; Keles, Umur LU ; Talib, S Zakiah A ; Ow, Jin Rong ; Tabaglio, Tommaso ; Goh, Christine M F ; Zhao, Li Na LU and Guccione, Ernesto , et al. (2025) In Journal of Cell Science
Abstract

In most mammals, the cell cycle kinase; cyclin-dependent kinase 2 (CDK2) is expressed as two major isoforms due to alternative splicing. The shorter CDK2 isoform: CDK2S, is expressed constitutively during the cell cycle and can be detected in several tissues. In contrast, the longer isoform: CDK2L, shows preferential expression in meiotically dividing cells and upon S-phase entry in the mitotic cycle. Both CDK2L and CDK2S form heteromeric complexes with cyclins A2 and E1 in vitro. However, complexes comprised of each isoform differ considerably in their kinase activity towards known CDK substrates. It is currently unknown whether the long and short isoforms of CDK2 play functionally different roles in vivo during either mitotic and... (More)

In most mammals, the cell cycle kinase; cyclin-dependent kinase 2 (CDK2) is expressed as two major isoforms due to alternative splicing. The shorter CDK2 isoform: CDK2S, is expressed constitutively during the cell cycle and can be detected in several tissues. In contrast, the longer isoform: CDK2L, shows preferential expression in meiotically dividing cells and upon S-phase entry in the mitotic cycle. Both CDK2L and CDK2S form heteromeric complexes with cyclins A2 and E1 in vitro. However, complexes comprised of each isoform differ considerably in their kinase activity towards known CDK substrates. It is currently unknown whether the long and short isoforms of CDK2 play functionally different roles in vivo during either mitotic and meiotic divisions as conventional knockout methodology deletes both of the isoforms. Therefore, we generated mice expressing only CDK2S or CDK2L and found that both CDK2L and CDK2S are sufficient to support both mitotic and meiotic division when expressed in the absence of the other. This data contributes to the explanation of the apparent tolerance of the evolutionary loss of CDK2L expression in humans.

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organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Journal of Cell Science
publisher
Company of Biologists Ltd
external identifiers
  • pmid:40977277
ISSN
0021-9533
DOI
10.1242/jcs.264291
language
English
LU publication?
yes
additional info
© 2025. Published by The Company of Biologists.
id
4699ad64-5cf9-45a5-bc30-01e935539262
date added to LUP
2025-09-26 08:44:43
date last changed
2025-09-27 03:22:26
@article{4699ad64-5cf9-45a5-bc30-01e935539262,
  abstract     = {{<p>In most mammals, the cell cycle kinase; cyclin-dependent kinase 2 (CDK2) is expressed as two major isoforms due to alternative splicing. The shorter CDK2 isoform: CDK2S, is expressed constitutively during the cell cycle and can be detected in several tissues. In contrast, the longer isoform: CDK2L, shows preferential expression in meiotically dividing cells and upon S-phase entry in the mitotic cycle. Both CDK2L and CDK2S form heteromeric complexes with cyclins A2 and E1 in vitro. However, complexes comprised of each isoform differ considerably in their kinase activity towards known CDK substrates. It is currently unknown whether the long and short isoforms of CDK2 play functionally different roles in vivo during either mitotic and meiotic divisions as conventional knockout methodology deletes both of the isoforms. Therefore, we generated mice expressing only CDK2S or CDK2L and found that both CDK2L and CDK2S are sufficient to support both mitotic and meiotic division when expressed in the absence of the other. This data contributes to the explanation of the apparent tolerance of the evolutionary loss of CDK2L expression in humans.</p>}},
  author       = {{Palmer, Nathan and Kalem-Yapar, Nisan Ece and Hultén, Hanna and Keles, Umur and Talib, S Zakiah A and Ow, Jin Rong and Tabaglio, Tommaso and Goh, Christine M F and Zhao, Li Na and Guccione, Ernesto and Liu, Kui and Kaldis, Philipp}},
  issn         = {{0021-9533}},
  language     = {{eng}},
  month        = {{09}},
  publisher    = {{Company of Biologists Ltd}},
  series       = {{Journal of Cell Science}},
  title        = {{Differential splice isoforms of mouse CDK2 play functionally redundant roles during mitotic and meiotic division}},
  url          = {{http://dx.doi.org/10.1242/jcs.264291}},
  doi          = {{10.1242/jcs.264291}},
  year         = {{2025}},
}