This entry represents protein LIN-9/ALWAYS EARLY (LIN-9/ALY). LIN-9 from Caenorhabditis elegans is a homologue of the Drosophila always early (ALY) protein, which functions as a repressor of cell cycle regulated genes [, ].LIN-9 is a component of the evolutionary conserved DREAM (MuvB/DRM) complex, which represses transcription []. DREAM complex undergoes a cell cycle dependent switch of subunits. DREAM core bindsto the E2F4 transcription factor and to the RBL2 (p130) in quiescent cells, while associates with the transcription factor B-MYB in the S-phase []. In humans, LIN-9 acts as a tumor suppressor and plays a role in the expression of genes required for the G1/S transition [, ]. In pluripotent embryonic stem cells (ESC), LIN-9 plays an important role for proliferation and genome stability by activating genes with important functions in mitosis and cytokinesis [].In Arabidopsis thaliana, ALY is expressed ubiquitously in vegetative and reproductive tissues [].
This entry represents the retinoblastoma protein family, including retinoblastoma-associated protein (RB, also known as pRb, RB, p1051), retinoblastoma-like protein 1 (RBL1, also known as p107) and retinoblastoma-like protein 2 (RBL2, also known as RB2 or p130). Members of this family contain a conserved domain named the 'pocket' that interacts with the LXCXE motif found in viral proteins, such as SV40 large T antigen []. Therefore, this family is also called the pocket protein family.In humans, RB is a tumour suppressor linked to several major cancers []. RB forms complexes with E2Fs and represses gene expression by recruiting chromatin remodeling factors, such as histone deacetylases (HDACs) to E2F-responsive promoters [, ]. This interaction regulates genes necessary for DNA replication and cell cycle. Phosphorylation of RB family by CDK and cyclin complexes leads to release of the repressor complex and enables E2F-dependent gene expression []. Apart from E2Fs, RB also interacts with other transcription factors that govern cell differentiation [, ]. RBL1 and RBL2 are the components of the DREAM complex, which represses cell cycle-dependent genes in quiescent cells and plays a role in the cell cycle-dependent activation of G2/M genes [, ].
The tubulin heterodimer consists of one alpha- and one beta-tubulin polypeptide. In humans, five tubulin-specific chaperones termed TBCA/B/C/D/E are essential for bring the alpha- and beta-tubulin subunits together into a tightly associated heterodimer. Following the generation of quasi-native beta- and alpha-tubulin polypeptides (via multiple rounds of ATP-dependent interaction with the cytosolic chaperonin), TBCA and TBCB bind to and stabilise newly synthesised beta- and alpha-tubulin, respectively. The exchange of beta-tubulin between TBCA and TBCD, and of alpha-tubulin between TBCB and TBCE, resulting in the formation of TBCD/beta and TBCE/alpha. These two complexes then interact with each other and form a supercomplex (TBCE/alpha/TBCD/beta). Interaction of the supercomplex with TBCC causes the disassembly of the supercomplex and the release of E-site GDP-bound alpha/beta tubulin heterodimer, which becomes polymerization competent following spontaneous exchange with GTP [].This entry represents tubulin binding cofactor A (TBCA) from animal, plants and fungi. Human TBCA functions as a molecular chaperone for beta-tubulin []. Budding yeast TBCA, also known as Rbl2, may bind transiently to free beta-tubulin, which then passes into an aggregated form that is not toxic []. The sequence identity of Rbl2 and human TBCA is only 32%, they appear to be structurally distinct and may interact with beta-tubulin by different mechanisms [].
The tubulin heterodimer consists of one alpha- and one beta-tubulin polypeptide. In humans, five tubulin-specific chaperones termed TBCA/B/C/D/E are essential for bring the alpha- and beta-tubulin subunits together into a tightly associated heterodimer. Following the generation of quasi-native beta- and alpha-tubulin polypeptides (via multiple rounds of ATP-dependent interaction with the cytosolic chaperonin), TBCA and TBCB bind to and stabilise newly synthesised beta- and alpha-tubulin, respectively. The exchange of beta-tubulin between TBCA and TBCD, and of alpha-tubulin between TBCB and TBCE, resulting in the formation of TBCD/beta and TBCE/alpha. These two complexes then interact with each other and form a supercomplex (TBCE/alpha/TBCD/beta). Interaction of the supercomplex with TBCC causes the disassembly of the supercomplex and the release of E-site GDP-bound alpha/beta tubulin heterodimer, which becomes polymerization competent following spontaneous exchange with GTP [].This entry represents tubulin binding cofactor A (TBCA) from animal, plants and fungi. Human TBCA functions as a molecular chaperone for beta-tubulin []. Budding yeast TBCA, also known as Rbl2, may bind transiently to free beta-tubulin, which then passes into an aggregated form that is not toxic []. The sequence identity of Rbl2 and human TBCA is only 32%, they appear to be structurally distinct and may interact with beta-tubulin by different mechanisms []. The structure of TBCA has three helices forming a bundle closed fold with left-handed twist topology going up-and-down.
