Cloning, Expression, Purification and Crystallization of the PR Domain of Human Retinoblastoma Protein-Binding Zinc Finger Protein 1 (RIZ1)

Sun, Wanpeng

doi:10.3390/ijms9060950

Cited by 3 publications

(4 citation statements)

References 18 publications

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“…According to Sun Theory, the current human species, Homo sapiens, originated from a handful of survivors after a worldwide disaster. Then, through evolution, human reaches today's stage, the modern civilization, a critical stage, where things can happen into both directions, either toward better civilization or back to stone age or even extinction -like the nuclear wipe-down happened in Mars [10][11][12][13][14][15][16][17][18]. Moreover, the Sun Model of Civilization and Sun Evolution Theory can well interpret many ab-normal observations, novel discoveries and historical paradoxes.…”

Section: Discussionmentioning

confidence: 99%

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Solving the Darwinian Paradoxes by “Sun Model of Civilization”, Re-Examine the Origin Of Human

Sun

2024

JAAS

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There are many paradoxes according to Darwinian evolution theory. For example, homosexuality is influenced by gene. The same sex sexual behavior provides neither reproductive nor survival benefit according to Darwinian theory. This is called a Darwinian Paradox. Hereby, we propose a better theory, named Sun Theory of Evolution, to explain the Darwinian Paradoxes like that. In the Sun Theory, animals cannot evolve into human beings. Humans are intelligent beings since the beginning of the time when the earth entered a stable stage. According to Sun Theory, the current human species, Homo sapiens, originated from a handful of survivors after a worldwide disaster, like a global flood or a destructive war. Moreover, this unique theory supports and extends the Albert Einstein's most famous proverb: "I know not with what weapons World War III will be fought, but World War IV will be fought with sticks and stones." A severe war brought civilization down to the Stone Age, and human society had to restart again. Further, we proposed our new human evolution/civilization model, "Sun Model of Civilization". Based on the new model and novel theory, human has high-level of prehistorical civilization, a global disaster destroyed the records, and made it "prehistorical". Civilization may have repeating cycles, and this explains many abnormal observations. In Sun Theory, the Stone Age is around the bottom of the curve and is a gap period between two better civilization stages. It is a difficult age for humans, who go down to the bottom and survive in very harsh natural environments with minimal tools. It is noteworthy that it is extremely rare for a highly civilized human to become fossil, because he knows to avoid the dangerous marshland and the body is usually cremated when he die. This explains that there are lack of human fossils beyond the Stone Age. In addition, the current Carbon-14 dating, the major radioisotope experiment used to measure the archaeology time for human origins, is only reliable for up to 60,000 years. Further, radioisotope dating is not accurate if there are changes in environments, e.g. isotope deficiency in habitats, carbon ratios from nuclear activities and fossil fuel burning. Thus, the current dating methods are not ready to study human relics beyond the Stone Age. Unfortunately, such technical limits are often ignored because of the influences from the dominating belief, the Darwinian evolution.

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Section: Discussionmentioning

confidence: 99%

“…Hereby, we speculate a way to prove that our theory is better: in a genetic lab, we usually add some tags for genes. Very often, we add His tag to the genes of recombinant proteins for the downstream extraction purposes [15][16][17]. Natural beings do not have such His tag.…”

Section: Figurementioning

confidence: 99%

Solving the Darwinian Paradoxes by “Sun Model of Civilization”, Re-Examine the Origin Of Human

Sun

2024

JAAS

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“…According to a genetic perspective, RIZ1 may be downregulated by chromosomal instability and microsatellite instability, as well as frame-shift mutations, point mutations, and heterozygote deficiency. [25][26][27] From an epigenetic perspective, the deactivation of RIZ1 may occur due to promoter methylation and histone acetylation. The RIZ1 promoter has been demonstrated to have the characteristics of a CpG island, which suggests that RIZ1 is a target of inactivation by epigenetic mechanisms.…”

Section: Discussionmentioning

confidence: 99%

RIZ1 and histone methylation status in pituitary adenomas

Xue

Chen

et al. 2017

Tumour Biol.

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RIZ1 displays strong tumor-suppressive activities, which has a potential histone methyltransferase activity. The objective of the study was to evaluate the level and the methylation status of RIZ1 and analyze its association with clinicopathological features and the histone in the pituitary adenomas. We found that RIZ1-positive cases were 11/50 and H-Scores 22.75 ± 11.83 in invasive pituitary adenomas and 26/53 and 66.3 ± 21.7 in non-invasive pituitary adenomas (χ = 8.182, p = 0.004). RIZ1 and C-myc showed the opposite trend in these cases. The methylation levels of RIZ1 were more than 50% in 30.4% (7/23) CpG sites through MALDI-TOF Mass array. There was significant difference (p < 0.01) in 4 CpG sites between invasive pituitary adenoma group and non-invasive pituitary adenoma group; furthermore, the relieved methylation levels of H3K4/H3K9 and enhanced methylation levels of H3K27 in the patients' serum were found. Furthermore, there was statistic difference of H3K4 and H3K27 methylation between invasive pituitary adenoma and non-invasive pituitary adenoma group (p < 0.01). The average progression-free survival in high RIZ1 group was 52.63 ± 7.62 months and 26.06 ± 4.23 months in low RIZ1 group (p < 0.05). Promoter region methylation of RIZ1 may play an important role in the epigenetic silencing of RIZ1 expression in pituitary adenomas, which may translate into important diagnostic and therapeutic applications.

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“…A PR‐less oncogenic isoform has also been identified. Similar to other PRDMs (i.e., PRDM1α/β, PRDM3/EVI1, and PRDM16/MEL1), these two isoforms (named RIZ1 and RIZ2) have opposing functions in cancer and are expressed in different contexts [63–68]. While the predicted ZNF recognition motif is [TCxTCxGAGGxACT], whether PRDM2 binds directly to DNA remains to be explored.…”

Section: Znf Arrays and Dna‐binding Selectivitymentioning

confidence: 99%

The duality of PRDM proteins: epigenetic and structural perspectives

et al. 2021

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PRDMs are a subfamily of Kruppel-like zinc finger proteins controlling key processes in metazoan development and in cancer. PRDMs exhibit unique dualities: (i) PR domain/ZNF arraystheir structure combines a SET-like domain known as a PR domain, typically found in methyltransferases, with a variable array of C2H2 zinc fingers (ZNF) characteristic of DNA-binding transcription factors; (ii) Transcriptional activators/repressors -their physiological function is context and cell dependent; mechanistically, some PRDMs have a PKMT activity and directly catalyze histone lysine methylation, while others are rather pseudomethyltransferases and act by recruiting transcriptional co-factors; (iii) Oncogenes/tumor suppressors -their pathological function depends on the specific PRDM isoform expressed during tumorigenesis. This duality is well known as the "Yin and Yang" of PRDMs and involves a complex regulation of alternative splicing or alternative promoter usage, to generate full-length or PR-deficient isoforms with opposing functions in cancer. In conclusion, once their dualities are fully appreciated, PRDMs represent a promising class of targets in oncology by virtue of their widespread upregulation across multiple tumor types and their somatic dispensability, conferring a broad therapeutic window and limited toxic side effects. The recent discovery of a first-in-class compound able to inhibit PRDM9 activity has paved the way for the identification of further small molecular inhibitors able to counteract PRDM oncogenic activity.

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Cloning, Expression, Purification and Crystallization of the PR Domain of Human Retinoblastoma Protein-Binding Zinc Finger Protein 1 (RIZ1)

Cited by 3 publications

References 18 publications

Solving the Darwinian Paradoxes by “Sun Model of Civilization”, Re-Examine the Origin Of Human

Solving the Darwinian Paradoxes by “Sun Model of Civilization”, Re-Examine the Origin Of Human

RIZ1 and histone methylation status in pituitary adenomas

The duality of PRDM proteins: epigenetic and structural perspectives

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