The G1/S cell cycle checkpoints control whether eukaryotic cells enter the S phase (synthesis phase) of DNA synthesis through the G1 phase. Two cell cycle kinase complexes, CDK4/6-Cyclin D and CDK2- Cyclin E, work together to relieve the inhibition of dynamic transcriptional complexes containing retinoblastoma protein (Rb) and E2F. In cells undefined during the G1 phase, hypophosphorylated Rb binds to the E2F-DP1 transcription factor and forms an inhibitory complex with HDAC, thereby inhibiting downstream key transcriptional activities. Clear entry into the S phase is achieved by continuous phosphorylation of Rb by Cyclin D-CDK4/6 and Cyclin E-CDK2, which separates the transcription factor E2F from the inhibitory complex and allows transcription of the gene required for DNA replication. After the growth factor disappears, the expression level of cylin D is down-regulated by down-regulation of protein expression and phosphorylation-dependent degradation.
The Hippo signal is very conservative in evolution. It regulates organ size and tissue stability by regulating cell proliferation, apoptosis, and stem cell renewal. The core process of Hippo signaling is a kinase tandem process, Mst1/2 and Sav1 form a complex, phosphorylate and activate Lats1/2; Lats1/2 kinase then phosphorylates and inhibits transcriptional coactivators Yap and Taz. Yap and Taz are the most important effectors downstream of the Hippo pathway. Upon dephosphorylation, Yap and Taz translocate to the nucleus and interact with TEAD1-4 or other transcription factors (such as CTGF) to induce gene expression, thereby initiating cell proliferation and inhibiting apoptosis.
The scientific community operates on a self-correcting model that relies on repetition and replication. However, according to a 2016 survey by Nature, more than 70% reported to have failed to replicate experiments from another scientist, more than 50% reported failure in replicating his/her own experiment. Out of the 1,576 scientists surveyed, 906 were from biology or medicine disciplines.