What Is the Ubiquitination of Proteins?

Ubiquitination refers to the process of ubiquitin (a class of low-molecular-weight proteins) molecules that classify proteins in cells under the action of a series of special enzymes, select target protein molecules, and specifically modify target proteins. These special enzymes include ubiquitin activating enzymes, binding enzymes, ligases and degrading enzymes. Ubiquitination plays a very important role in protein localization, metabolism, function, regulation and degradation. At the same time, it also participates in the regulation of almost all life activities such as cell cycle, proliferation, apoptosis, differentiation, metastasis, gene expression, transcriptional regulation, signal transmission, damage repair, and inflammatory immunity. Ubiquitination is closely related to the pathogenesis of tumors and cardiovascular diseases. Therefore, as a major achievement of biochemical research in recent years, it has become a new target for research and development of new drugs.

Ubiquitination

Ubiquitination means

The change of p53 stability is closely related to its functional regulation. Tightly regulating the metabolic stability of p53 is very important for the growth and development of normal cells. p53 is a short half-life transcription factor, and the conversion of p53 protein is regulated by a ubiquitin-dependent proteolytic pathway [3]. The results of this study indicate that the degradation-related fragment of the p53 N-terminus cannot be separated from its transcriptionally active fragment; inhibition or destruction of the ubiquitin proteasome hydrolysis pathway has no universal effect on the transcription reaction, but can specifically inhibit the transcription response of p53. The very interesting finding of this study is that in the presence of a proteasome inhibitor or the absence of a ubiquitination pathway, p53 stability is enhanced, and intracellular p53 protein levels are increased, but p53 transcriptional activity is reduced. That is, when the ubiquitin proteasome hydrolysis pathway is inhibited, the transcriptional function of p53 is also destroyed, indicating that the proteolytic pathway of p53 is necessary for its transcription reaction, and there is a functional relationship between the two processes. This finding suggests that the protein degradation pathway regulated by the ubiquitin proteasome plays an important role in p53 transcription. In previous studies, the same pattern was found in the thyroid receptor and estrogen-regulated transcription process [1 0, 1 1]. We speculate that at least some of the intracellular active proteins, the ubiquitin proteasome hydrolysis pathway, play an important role in transcriptional activation and gene expression regulation. This discovery will be of great significance for the regulation of cell growth, differentiation, and diagnosis and treatment of diseases, such as retaining p53 activity, and preventing and treating tumors.

The biochemical relationship between p53 ubiquitin proteolysis and transcription activation is not clear. Research supports the hypothesis that certain cytokines link and participate in these two processes. Studies have shown that the transcriptional co-activator p3 0 0 / CBP plays an important role in the transcription response of p53, and the p3 0 0 / mdm2 complex also participates in the degradation of p53 regulated by mdm2. P53, mdm2, and p3 0 0C / H1 are specific Sexual interaction is an important step in the process of p53 conversion regulated by mdm2 [1 3]. We found in a recent study that p3 0 0 plays an important role in mdm2 regulated p53 conversion by linking ubiquitination and degradation processes [6]. The above results suggest that the transcription activating factor p3 0 0 / CBP is of great significance in the intracellular connection of p53 ubiquitin proteolysis and transcription activation. Of course, we cannot rule out the role of other cytokines such as mdm2 in this process. The detailed molecular mechanism needs further study.

---- Article from (Progress in Anatomical Sciences, Vol. 4, 2002, Volume 4, Department of Pharmacology, Dalian Medical University; Department of Cell Biochemistry, Ohio State University; Department of Biochemistry, Dalian Medical University, Dalian 116027, China; Yao Jihong; Qianzheng Zhu; AA Wani; Yang Peiman (Cui Xiuyun)

When Damaged DNA is activated, ATM is activated, which activates p53 by phosphorylation. Phosphorylated p53 causes cells to arrest growth in G1 phase for DNA repair. If the repair fails, the bax gene is activated to allow cells to undergo apoptosis to ensure the genetic stability of the genome.

P53-dependent cyclin-dependent kinase (CDK) suppressor P21 and DNA repair genes (growth arrest and DNA damage 45, GASS45) up-regulated sexual transcription. Note: Not shown in GASS45.

The Rb protein is activated by dephosphorylation and binds to the E2F family, blocking the transcription of S-phase genes on DNA. In contrast, the phosphorylated Rb protein is separated from E2F, so that E2F and DP1 protein form a heterodimer, activating the transcription of S-phase genes. Note: DP1 is not marked.

Cyclin D1 phosphorylates Rb protein by interacting with CDK4 kinase, and regulates the transition of cell cycle G1 ~ S. It is a key protein for G1 cell proliferation. PCNA promotes this carcinogenic process.

Bcl-2 (B-cell lymphoma / leukemia, bcl), a member of this family mainly inhibits apoptosis rather than promotes cell proliferation.