Examination of human B cell-derived lines revealed specific phenotype-related differences in D-type cyclin expression ( 17, 18). Consistent with this idea, stimulation of B cells with complete versus partial activation signals suggests that signals responsible for moving B cells through the restriction point impact at the level of cyclin D2 protein accumulation ( 14, 16).ДЇurther evidence suggesting discrete roles for D-type cyclins in B cells comes from studies of cyclin expression in B leukemia and lymphomas representative of different B cell subsets. Our laboratory has demonstrated that proliferating B lymphocytes express both cyclin D2 and D3 but not D1 ( 14) however, it is the accumulation of cyclin D2 which has been suggested to be the critical event in passage through the restriction point ( 15). However, there are specific lines of evidence in certain cell types suggesting that an individual D-type cyclin has distinct biological roles during certain cell cycles ( 8, 9) and that D-type cyclins may have specific roles in cellular processes other than proliferation ( 10вЂ“ 13). More direct evidence for overlapping roles of D cyclins in proliferation is the ability of cyclins D1, D2 or D3 to restore a normal cycle progression time to a cyclin D1-deficient subline of DT40 ( 7). Results from mice homologous for genetic disruptions in cyclins D1 or D2 suggest that D cyclin function is overlapping and potentially redundant since viable offspring were obtained in each case ( 5, 6). The three D-type cyclins, D1, D2 and D3, are expressed in proliferating cells in a lineage-specific manner with at least two different D-type cyclins being expressed in most cell types. Consistent with their major role in the positive regulation of G 1, the D-type cyclins are required for S phase entry, and their overexpression both accelerates G 1 and reduces the dependence on exogenous growth factors ( 4).

The D-type cyclins are the first components of the cell cycle machinery to become induced in response to mitogen stimulation ( 1вЂ“ 3), and their associated kinase activity has a critical role in the commitment to enter S phase by phosphorylating and thereby inactivating pRb, a negative regulator of cell cycle progression ( 3). Operationally, the restriction point separates the cell cycle into an initial mitogen-dependent period followed by a growth factor-independent stage ( 1вЂ“ 3). The commitment to enter S phase and divide or remain in the G 1 phase with an unduplicated genome takes place in mid-to-late G 1 and is referred to as the restriction point (R) ( 1вЂ“ 3). CLL chronic lymphocytic leukemia, HRP horseradish peroxidase, LPS lipopolysaccharide, PE phycoerythrin Introduction

Issues with bcr 2000