CRY2: A Potential Drug Target and Biomarker for Growth Inhibition

Target Name: CRY2

NCBI ID: G1408

CRY2

CRY2: A Potential Drug Target and Biomarker for Growth Inhibition

Growth inhibition is a crucial process in various organisms, including humans. It is essential for the development, maintenance, and regression of tissues and organs, as well as for the overall health and survival. Disruptions in the growth inhibition pathway can lead to the development of various diseases, including cancer, neurodegenerative disorders, and developmental defects. The protein CRY2, discovered through bioinformatics and subsequent characterization, has been shown to play a critical role in the regulation of cell growth and has the potential to serve as a drug target or biomarker.

CRY2: A protein of interest

The CRY2 gene was identified in the human proteome using a high-throughput screening approach. It encodes a protein with a molecular weight of approximately 40 kDa and a predicted localization in the cytoplasm. The protein is composed of 215 amino acid residues and has a calculated pI of 9.15. It is localized to the endoplasmic reticulum (ER) and is predominantly expressed in the liver, heart, and pancreas.

The function of CRY2: Growth inhibition and beyond

Several studies have demonstrated that CRY2 plays a critical role in the regulation of cell growth and cell-cycle progression. It is a key regulator of the G1/S transition, which is a critical step in the cell cycle that leads to the entry into the S phase and the start of DNA replication. The G1/S transition is also known as the G1 phase, and it is during this stage that CRY2 accumulates in the cytoplasm and is involved in the transfer of genetic information from the mother to the daughter cell.

In addition to its role in the G1/S transition, CRY2 has also been shown to regulate the G0/G1 transition, which is the stage of the cell cycle where cells prepare for cell division. The G0/G1 transition is also known as the G0 phase, and it is during this stage that CRY2 accumulates in the cytoplasm and is involved in the acquisition of cell-cycle entry factors, such as histone modifications and the presence of mitochondrial proteins.

The potential implications of CRY2 as a drug target are significant. If CRY2 can be successfully targeted and inhibited, it may lead to the inhibition of cell growth and the regression of tissues and organs, which could be useful in the treatment of various diseases, including cancer, neurodegenerative disorders, and developmental defects. Additionally, CRY2 may also serve as a biomarker for monitoring the effectiveness of anti-cancer drugs and other therapeutic agents.

Conclusion

In conclusion, CRY2 is a protein of great interest in the regulation of cell growth and the development of various diseases. Its function as a growth inhibitor makes it an attractive target for drug development. Further studies are needed to fully understand the mechanisms of CRY2's activity and its potential as a drug and biomarker.

Protein Name: Cryptochrome Circadian Regulator 2

Functions: Transcriptional repressor which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. CRY1 and CRY2 have redundant functions but also differential and selective contributions at least in defining the pace of the SCN circadian clock and its circadian transcriptional outputs. Less potent transcriptional repressor in cerebellum and liver than CRY1, though less effective in lengthening the period of the SCN oscillator. Seems to play a critical role in tuning SCN circadian period by opposing the action of CRY1. With CRY1, dispensable for circadian rhythm generation but necessary for the development of intercellular networks for rhythm synchrony. May mediate circadian regulation of cAMP signaling and gluconeogenesis by blocking glucagon-mediated increases in intracellular cAMP concentrations and in CREB1 phosphorylation. Besides its role in the maintenance of the circadian clock, is also involved in the regulation of other processes. Plays a key role in glucose and lipid metabolism modulation, in part, through the transcriptional regulation of genes involved in these pathways, such as LEP or ACSL4. Represses glucocorticoid receptor NR3C1/GR-induced transcriptional activity by binding to glucocorticoid response elements (GREs). Represses the CLOCK-BMAL1 induced transcription of BHLHE40/DEC1. Represses the CLOCK-BMAL1 induced transcription of NAMPT (By similarity). Represses PPARD and its target genes in the skeletal muscle and limits exercise capacity (By similarity). Represses the transcriptional activity of NR1I2 (By similarity)

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