Members of this vertebrate family of proteins are targets for phosphorylation by CDK1 and casein kinase [, ]. They are also phosphorylated upon DNA damage, probably by ATM or ATR [].
Leucine zipper putative tumor suppressor 1 (LZTS1, FEZ1) plays a role in mitosis []. It is associated with assembled microtubules and is involved in the stabilization of active p34CDC2 (Cdk1) []. LZTS1 plays an important role in ensuring proper Cdk1 activity during M phase. By maintaining high levels of Cdk1 activity, it prevents chromosomes missegregation []. LZTS1 plays an important role in human carcinogenesis [, , ].
Filamin family consists of Filamin-A (FLN-A), Filamin-B (FLN-B) and Filamin-C (FLN-C). They are a group of actin binding proteins that may be involved in actin microfilaments organisation [].This entry represents filamin B, which transduces signals from various membrane receptors and intracellular proteins onto the actin cytoskeleton []. In humans it regulates chondrocyte proliferation and differentiation through Cdk1 signalling [].
Speedy (Spy1, also known as RINGO A) is a cell cycle regulatory protein which binds and activates CDK1 and CDK2 [], protein kinases that allows progression through G1/S phase and further replication events. Spy1 activates CDK2 inducing a conformational change of the CDK2 T-loop that avoids its phosphorylation []. Spy1 expression overcomes a p27-induced cell cycle arrest to allow for DNA synthesis, so cell cycle progression occurs due to an interaction between Spy1 and p27 [].
This entry represents eukaryotic proteins that contain a domain of approximately 40 amino acids in length. These proteins are found in association with . There are two conserved sequence motifs: TPVCTP and LERRKS. This domain is found on the human nucleolar protein hNIFK. It binds to the fork-head-associated domain of human Ki67. High-affinity binding requires sequential phosphorylation by two kinases, CDK1 and GSK3, yielding pThr238, pThr234 and pSer230. This interaction is involved in cell cycle regulation [].
This entry represents M-phase-specific PLK1-interacting protein and related uncharacterised sequences from vertebrates.M-phase-specific PLK1-interacting protein (also known as TTD non-photosensitive 1 protein, TTDN1) may play a role in maintenance of cell cycle integrity by regulating mitosis or cytokinesis []. Its The subcellular location is regulated during cell cycle. During interphase, it is located in the nucleus. During mitosis, it is located at the centrosome and dispersed in the cytoplasm. During telophase, it is located in the midbody. It colocalizes with PLK1 at the centrosome in M phase [, ]. It is phosphorylated during mitosis in the cell cycle probably by CDK1 [, ]. Defects in MPLKIP are a cause of trichothiodystrophy non-photosensitive type 1 (TTDN1); also known as Amish brittle hair brain syndrome (ABHS), hair-brain syndrome and BIDS syndrome. TTDN1 is an autosomal recessive disorder characterised by short stature, intellectual impairment, sulfur-deficient brittle hair and decreased male fertility but not cutaneous photosensitivity [].
Checkpoint kinase 1 (Chk1) is a serine/threonine kinase implicated in many major checkpoints of the cell cycle, providing a link between upstream sensors and the cell cycle engine. It plays an important role in DNA damage response and maintaining genomic stability [, , ]. Chk1 acts as an effector of the sensor kinase, ATR (ATM and Rad3-related), a member of the PI3K family, which is activated upon DNA replication stress []. Chk1 delays mitotic entry in response to replication blocks by inhibiting cyclin dependent kinase (Cdk) activity. In addition, Chk1 contributes to the function of centrosome and spindle-based checkpoints, inhibits firing of origins of DNA replication (Ori), and represses transcription of cell cycle proteins including cyclin B and Cdk1 [, ].
This is the middle domain of the H2 subunit of the condensin II complex, found in eukaryotes but not fungi. This region represents the disordered section of CNDH2 between the N- and the C-terminal domains.Eukaryotes carry at least two condensin complexes, I and II, each made up of five subunits. The functions of the two complexes are collaborative but non-overlapping. CI appears to be functional in G2 phase in the cytoplasm beginning the process of chromosomal lateral compaction while the CII are concentrated in the nucleus, possibly to counteract the activity of cohesion at this stage. In prophase, CII contributes to axial shortening of chromatids while CI continues to bring about lateral chromatid compaction, during which time the sister chromatids are joined centrally by cohesins. There appears to be just one condensin complex in fungi. CI and CII each contain SMC2 and SMC4 (structural maintenance of chromosomes) subunits, then CI has non-SMC CAP-D2 (CND1), CAP-G (CND3), and CAP-H (CND2). CII has, in addition to the two SMCs, CAP-D3, CAPG2 and CAP-H2. All four of the CAP-D and CAP-G subunits have degenerate HEAT repeats, whereas the CAP-H are kleisins or SMC-interacting proteins (ie they bind directly to the SMC subunits in the complex). The SMC molecules are each long with a small hinge-like knob at the free end of a longish strand, articulating with each other at the hinge. Each strand ends in a knob-like head that binds to one or other end of the CAP-H subunit. The HEAT-repeat containing D and G subunits bind side-by-side between the ends of the H subunit. Activity of the various parts of the complex seem to be triggered by extensive phosphorylations, eg, entry of the complex, in Sch.pombe, into the nucleus during mitosis is promoted by Cdk1 phosphorylation of SMC4/Cut3; and it has been shown that Cdk1 phosphorylates CAP-D3 at Thr1415 in He-La cells thus promoting early stage chromosomal condensation by CII [, ].
This entry represents the N-terminal domain of the H2 subunit of the condensing II complex, found in eukaryotes but not in fungi. Eukaryotes carry at least two condensin complexes, I and II, each made up of five subunits. The functions of the two complexes are collaborative but non-overlapping. CI appears to be functional in G2 phase in the cytoplasm beginning the process of chromosomal lateral compaction while the CII is concentrated in the nucleus, possibly to counteract the activity of cohesion at this stage. In prophase, CII contributes to axial shortening of chromatids while CI continues to bring about lateral chromatid compaction, during which time the sister chromatids are joined centrally by cohesins. There appears to be just one condensin complex in fungi. CI and CII each contain SMC2 and SMC4 (structural maintenance of chromosomes) subunits, then CI has non-SMC CAP-D2 (CND1), CAP-G (CND3), and CAP-H (CND2). CII has, in addition to the two SMCs, CAP-D3, CAPG2 and CAP-H2. All four of the CAP-D and CAP-G subunits have degenerate HEAT repeats, whereas the CAP-H are kleisins or SMC-interacting proteins (ie they bind directly to the SMC subunits in the complex). The SMC molecules are each long with a small hinge-like knob at the free end of a longish strand, articulating with each other at the hinge. Each strand ends in a knob-like head that binds to one or other end of the CAP-H subunit. The HEAT-repeat containing D and G subunits bind side-by-side between the ends of the H subunit. Activity of the various parts of the complex seem to be triggered by extensive phosphorylations, eg, entry of the complex, in Sch.pombe, into the nucleus during mitosis is promoted by Cdk1 phosphorylation of SMC4/Cut3; and it has been shown that Cdk1 phosphorylates CAP-D3 at Thr1415 in He-La cells thus promoting early stage chromosomal condensation by CII [, ].
This entry includes cell division cycle-associated protein 3 (CDCA3; also known as trigger of mitotic entry protein 1 or TOME-1), which is required for entry into mitosis. The protein is found at high levels during the G2 and M phases of mitosis, but declines rapidly during the G2 phase. Entry into mitosis requires the relocalization to the nucleus and activation of cyclin-dependent kinase 1 (cdk1) by association with cyclin B, and exit from mitosis occurs when cyclin B is degraded and the kinase activity decreases. Anaphase promoting complex (APC) is an E3 ligase active during anaphase and G1, and is required for the degradation of cyclin B. CDCA3 is a cytosolic protein and a substrate of APC. It associates with Skp-1 and is required for the degradation of the cdk1 inhibitor wee1, a tyrosine kinase. Degradation of CDCA3 leads to an accumulation of wee1 during interphase []. The CDCA3 protein contains an F-box-like region and a KEN box; the latter is required for association with the APC complex.
Cyclin-dependent kinase 7 (CDK7) is a serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription. It is activated by binding to a cyclin; binding to a different cyclin and phosphorylation of another kinase progresses the cell cycle. CDK7 binds cyclin-B and phosphorylates CDK1 during G2-M transition, and phosphorylates CDK2 and binds to cyclins during G1-S transition [, ]. CDK7 phosphorylates and activates p53 following DNA damage [], but CDK7 is then inactivated by p53, which arrests the cell cycle, allowing the cell to recover or undergo apoptosis []. CDK7 is also the catalytic subunit of the CDK-activating kinase (CAK) complex, which also contains cyclin-H (CCNH) and MAT1 [, ]. In turn, the CAK associates with the core-TFIIH to form the TFIIH basal transcription factor [].This entry includes CDK7 from animals, Kin28 from budding yeasts and Crk1 (also known as Mcs6) from fission yeasts. S. pombe possesses two CAKs, the nonessential Csk1 and the essential Mcs6 kinases, corresponding to the yeast Cak1 and the metazoan CDK7, respectively. Mcs6 modulates gene expression through both its CAK and CTD kinase activities []. Kin28 is the closest homologue of CDK7 from budding yeasts. It forms a complex with Ccl1 and Tfb3. This complex associate with TFIIH for transcription regulating activity, but does not display CAK activity []. Instead, Cak1, a single-subunit kinase distantly related to Cdk, catalyzes Cdk activation at both transitions of the budding yeast cell cycle [].
