| Description: |
Cyclins are eukaryotic proteins that play an active role in controlling nuclear cell division cycles [], and regulate cyclin dependent kinases (CDKs). Cyclins, together with the p34 (cdc2) or cdk2 kinases, form the Maturation Promoting Factor (MPF). There are two main groups of cyclins, G1/S cyclins, which are essential for the control of the cell cycle at the G1/S (start) transition, and G2/M cyclins, which are essential for the control of the cell cycle at the G2/M (mitosis) transition. G2/M cyclins accumulate steadily during G2 and are abruptly destroyed as cells exit from mitosis (at the end of the M-phase). In most species, there are multiple forms of G1 and G2 cyclins. For example, in vertebrates, there are two G2 cyclins, A and B, and at least three G1 cyclins, C, D, and E.Cyclin homologues have been found in various viruses, including Saimiriine herpesvirus 2 (Herpesvirus saimiri) and Human herpesvirus 8 (HHV-8) (Kaposi's sarcoma-associated herpesvirus). These viral homologues differ from their cellular counterparts in that the viral proteins have gained new functions and eliminated others to harness the cell and benefit the virus [].Among G1 regulators, D-type cyclins serve as targets of growth factors to integrate extracellular signals into the core cell cycle regulators. D-type cyclins were identified in three independent approaches; (I) a target gene of chromosomal translocations in a variety of cancers [], (II) a mammalian cyclin gene that can complement yeast G1 cyclin deficiency [], and (III) a delayed early growth factor inducible gene []. D-type cyclins are composed of three different but closely related subfamilies (D1, D2, and D3), all differentially expressed in a wide variety of organs and in a tissue-specific manner. Expression of D-type cyclins is induced in response to a variety of mitogenic signals and they function as a regulatory subunit of cyclin-dependent kinases (Cdk).D-type cyclins can interact with 4 different Cdks (Cdk2, 4, 5, and 6), among which Cdk4 and Cdk6 are apparently the major functional catalytic partners in proliferating cells. When cells are exposed to growth factor stimulation, the expression of cyclin D is maintained regardless of the point in the cell cycle. However, accumulation of active cyclin D/Cdk4 (or Cdk6) complex is rate-limiting and is required for cells to progress through G1 and to commit to entering S phase. The over expression of D-type cyclins shortens the length of G1 without affecting remainder of the cell cycle. This event is clearly different from phenotype of the cells over expressing another G1 cyclin, cyclin E, in which G1 is shortened but elongation of the S phase compensates this shortening and as a result, doubling time of the cell remains unchanged. Thus, the cyclin D/Cdk4 complex largely exerts effects on commitment of cells for the S phase entry during the G1 phase, while functions of cyclin E/Cdk2 kinase are more directly involved in the initiation of chromosomal DNA synthesis [, ].This entry is comprised of D-type cyclins that are evolutionarily conserved across a variety of species. |
