The role of the Cdk9/Cyclin T1 complex in T cell differentiation.
The Cdk9/Cyclin T1 complex is very important in controlling specific differentiative pathways of several cell types, including muscle cells and neurons. We recently demonstrated the involvement of this complex in B cell activation/differentiation. To check whether the Cdk9/Cyclin T1 complex is also involved in the T cell activation/differentiation process, we isolated different T cell populations by magnetic separation, based on their surface antigens. We observed that the expression level of Cdk9/Cyclin T1 increases in effector T cells (CD27(+)), as well as in activated T cells (CD25(+)) and memory T cells (CD45RA(-)), thus suggesting a specific upregulation of the Cdk9/Cyclin T1 complex following antigen encounter. We have previously demonstrated that in B cells, Cdk9 interacts in vivo with the E2A gene products E12/E47 (members of the basic helix-loop-helix family) which are involved in differentiation. In this article, we show that this interaction also occurs in T cells. This suggests an active role for the Cdk9/Cyclin T1 complex during lymphoid differentiation, through physical binding with E12 and E47. These preliminary results suggest that the Cdk9/Cyclin T1 complex may be important in the activation and differentiation program of lymphoid cells and that its upregulation, which is due to still unknown mechanisms, may contribute to malignant transformation.
Leucci
Eleonora
E
Department of Human Pathology and Oncology, University of Siena, Siena, Italy.
De Falco
Giulia
G
Onnis
Anna
A
Cerino
Giovanna
G
Cocco
Mario
M
Luzzi
Anna
A
Crupi
Domenica
D
Tigli
Chiara
C
Bellan
Cristiana
C
Tosi
Piero
P
Leoncini
Lorenzo
L
Giordano
Antonio
A
D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D056906:Cyclin T; D042863:Cyclin-Dependent Kinase 9 / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007156:Immunologic Memory; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D015851:Interleukin-7 / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D019169:Jurkat Cells; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000032:analysis; D010703:Phorbol Esters / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051820:TCF Transcription Factors / Q000378:metabolism; D013997:Time Factors; D058125:Transcription Factor 7-Like 1 Protein; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis; D015854:Up-Regulation
C503684:CCNT1 protein, human; D056906:Cyclin T; D016213:Cyclins; D053645:Interleukin-2 Receptor alpha Subunit; D015851:Interleukin-7; D007476:Ionophores; D008562:Membrane Glycoproteins; D010703:Phorbol Esters; D012333:RNA, Messenger; D051820:TCF Transcription Factors; C544912:TCF7L1 protein, human; D058125:Transcription Factor 7-Like 1 Protein; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D015759:Ionomycin; C467969:CDK9 protein, human; D042863:Cyclin-Dependent Kinase 9; D017493:Leukocyte Common Antigens; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1