# The Less Known Cyclins--Uncovered
## 12 Cyclin T  
Cyclin T exists in two forms: cyclin T1 encoded by the CCNT1 gene and cyclin T2 encoded by CCNT2. In turn, cyclin T2 may be divided into cyclin T2a and T2b, which is the result of alternative splicing. Cyclin T in the N-terminal domain contains the \"cyclin box\" domain, which binds to the Cdk9 kinase and the C-terminal domain with PEST [98; 99; 100]. Similar to cyclin H, the level of cyclin T does not fluctuate during the cell cycle, suggesting that it performs functions that are not specific to the cell cycle. The mRNAs of cyclin T1 and T2 occur in all human tissues. It should be noted that tissues of mesenchymal origin, such as connective tissue, skeletal muscle, myocardial cells, adipocytes, chondrocytes and endothelial cells, and blood and lymphoid tissues, show high levels of cyclin T1 expression. In turn, T2a cyclin is extensively expressed in all cell types, although higher levels occur in some terminally differentiated tissues, such as muscle, blood, lymphoid and connective tissues [99; 100; 101].  
In humans, cyclin T (T1, T2a, T2b) together with Cdk9 form a complex called positive transcription elongation factor (P-TEFb), which participates in the regulation of transcription by RNA polymerase II [100]. The cyclin T itself, and the P-TEFb complex, plays an important role in normal and cancer cells. In healthy cells, the P-TEFb complex consisting of cyclin T and Cdk9 phosphorylates serine 2 in the CTD domain of RNA polymerase II to regulate the productive prolongation of transcription. [PERSON] et al., 1998 [102] showed that any of the three cyclin proteins (T1, T2a or T2b) complexed with Cdk9 forms the active molecule P-TEFb, which can phosphorylate CTD RNA polymerase II and cause DDR-sensitive (DNA damage response) transition from unsuccessful to productive elongation [102].  
Cyclin T in normal cells, in addition to the transcription process, is involved in the regulation of other cellular processes, such as the differentiation of muscle cells, presentation, and processing of antigen, or cell proliferation. [PERSON] et al., 2003 [99] confirmed that the high level of cyclin T2a expression occurs in mature muscle cells, while the peak is achieved during in vitro muscle differentiation. These data suggest that the cycT2a-Cdk9 may promote myogenic differentiation by inducing the expression of specific muscle genes [101]. In turn, [PERSON] et al., 2007 [103] demonstrated that the expression of cycT1-Cdk9 is a pivotal element of B-cell differentiation and activation. The level of the cycT1-Cdk9 grows in B-lymphocytes, and this process takes place through the reaction with the germinal center [104]. However, after the isolation of different T cell populations, the researchers also showed an increase in the expression level of the cycT1-Cdk9. This study confirms the increased expression of the complex in T and B-cells after encountering antigen [103].  
[PERSON] et al., 2002 [105] in studies involving human cell lines, and [PERSON] and [PERSON], showed that cyclin T in the complex with Cdk9 interacts with the Rb protein, which has a fundamental function in regulating the point controlling the transition between G1 and S phase. The role of the Rb protein is based on the transduction of the signal that connects the cell cycle control system with transcription [105]. In turn, phosphorylation of pRb protein mediated by CycT-Cdk9 is necessary for the cell cycle progression, suggesting an important role of the cyclin also in cancer cell proliferation. Moreover, [PERSON] et al., 2004 [106] observed an imbalance in cyclin T and Cdk9 mRNA levels in several types of hematopoietic tumors, such as follicular lymphoma, diffuse large B-cell lymphoma, [PERSON]'s lymphoma and [PERSON]'s lymphoma cell lines. Additionally, they detected high levels of cyclin T expression in lymphomas derived from B and T cell precursors [106].