Research Article

An Integrated Framework to Model Cellular Phenotype as a Component of Biochemical Networks

Table 1

Canonical functions of modelled genes in cell cycle regulation.

CLN1G1 cyclin: activates CDC28 kinase to promote the G1 to S phase transition; CLN-CDC28 complex enhances ubiquitin-mediated proteolysis of SIC1 by phosphorylation, regulates START-related events: budding, spindle-pole-body duplication, and DNA synthesis, and homologous with CLN2
CLN2 G1 cyclin: activates CDC28 kinase to promote the G1 to S phase transition; CLN-CDC28 complex enhances ubiquitin-mediated proteolysis of SIC1 by phosphorylation, regulates START-related events: budding, spindle-pole-body duplication, and DNA synthesis, and homologous with CLN1
CLN3 G1 cyclin: activates CDC28 kinase to promote the G1 to S phase transition and regulates transcription of CLN1 and CLN2
CyclinsCLB1 G2 cyclin: activates CDC28 kinase to promote the transition from G2 to M phase, promotes spindle elongation during mitosis, negatively regulates SBF-mediated transcription, and homologous with CLB2
CLB2 G2 cyclin: activates CDC28 kinase to promote the transition from G2 to M phase, promotes spindle elongation during mitosis, negatively regulates SBF-mediated transcription, and homologous with CLB1
CLB5 G1/S cyclin: activates CDC28 kinase to promote initiation of DNA synthesis, inactivated by SIC1, negatively regulates CLN-CDC28 complex formation, forms mitotic spindles in association with CLB3 and CLB4, and homologous with CLB6
CLB6 G1/S cyclin: activates CDC28 kinase to promote initiation of DNA synthesis, inactivated by SIC1, negatively regulates CLN-CDC28 complex formation, forms mitotic spindles in association with CLB3 and CLB4, and homologous with CLB6

CDCCDC6 ATP-binding protein required for DNA replication, component of the pre-replicative complex (pre-RC) which is required for MCM2-7 DNA association
CDC28 Cyclin-dependent kinase: alternately associates with G1 cyclins and G2/M cyclins, regulates spindle-pole-body duplication, budding, SIC1 proteolysis in association with CLN1-3, regulates DNA replication in association with CLB5-6, and regulates spindle assembly, inactivation of CLN transcription through repression of SBF transcription factor in association with CLB1-2

MCM1 Regulates expression of CLB1, CLB2, BUD4, SWI5 in M phase: CLN3, SWI4, CDC6 at M/G1 transition
SWI4 Transcription cofactor, forms complex with SWI6 and regulates transcription of CLN1-2; activity initiated by CLN3-CDC28, repressed by CLB2-CDC28
Transcription factorsSWI5 Activates transcription of SIC1 and CDC6 at the M/G1 phase boundary and in G1 phase; localization to the nucleus occurs during G1, regulated by CDC28-mediated phosphorylation
SWI6 Transcription cofactor: forms complexes with DNA-binding proteins SWI4 and MBP1 to regulate transcription at the G1/S transition and regulates transcription of CLN1-2, CLB5-6; localization regulated by phosphorylation; transcriptional activity initiated by CLN3-CDC28 complex, repressed by CLB2-CDC28 complex
MBP1 Transcription cofactor: forms complex with SWI6 and regulates transcription of CLB5-6

InhibitorsSIC1 Inhibits CLB5/6-CDC28 complex formation, inhibits G1/S transition, downregulates CLB-CDC28 activity in late stages of mitosis, targeted for ubiquitin-mediated proteolysis by CLN-CDC28
CDH1 Activates anaphase promoting complex/cyclosome (APC/C) and directs ubiquitinylation of cyclins, cell division cycle genes
CDC20 Activates anaphase-promoting complex/cyclosome (APC/C) and directs ubiquitination of CLB1-4, PDS1