Research has increasingly focused on transcription elongation factor B1 (TCEB1 or Elongin C) within renal cell carcinoma (RCC) because of its involvement with the VHL pathway and its role in both the ubiquitin-proteasome degradation system and cancer cell metabolic regulation. TCEB1 functions as a crucial protein that directs the transcription process in eukaryotic cells. The RNA polymerase II transcription complex includes this component which primarily drives the effective RNA polymerase II extension on the DNA template.
TCEB1 interacts with additional tumor-related genes to synergistically affect renal cell carcinoma formation and progression. Further research is required to determine how TCEB1 functions specifically in renal cell carcinoma. Research efforts in this field continue and we anticipate future discoveries to better understand TCEB1's function in renal cell carcinoma.
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Fig 1. TCEB1 mutations affect renal cell carcinoma (Hakimi, A., et al. 2015)
Physiological Functions of TCEB1
The protein TCEB1 facilitates transcription elongation as it increases RNA polymerase binding to DNA and stimulates transcription. The gene TCEB1 produces Elongin C protein that forms the VHL-E3 ubiquitin ligase complex with Elongin B and VHL protein which targets HIF (hypoxia-inducible factor) for degradation. In normal conditions TCEB1 helps stabilize the VHL complex which binds HIF-α leading to its degradation by the ubiquitin-proteasome system resulting in the inhibition of tumor angiogenesis glycolysis and cell proliferation. Mutations or the absence of TCEB1 disrupts the VHL complex function leading to enhanced HIF-α stability which allows cancer cells to better survive low-oxygen conditions and speeds up RCC progression.
Structure
TCEB1 carries distinct protein domains which enable interaction with various transcription factors and cofactors to regulate transcription.
Transcriptional Regulation
The protein TCEB1 ensures exact control of gene expression through the effective elongation of RNA polymerase II and plays roles in cell proliferation as well as differentiation while also enabling environmental response mechanisms.
Cell Cycle Control
The regulation of the cell cycle relies heavily on this process which plays a key role during cell proliferation and differentiation.
Response
Under various physiological and pathological stimuli including stress and specific signaling molecules TCEB1 modulates gene expression to help cells adapt.
Function of TCEB1, SASA Transcriptional Regulator
The function of TCEB1 within renal cell carcinoma (RCC) is becoming more widely studied. TCEB1 functions as a transcriptional regulator which might regulate gene expression patterns within tumor cells to influence their proliferation and movement as well as their ability to survive. Research indicates that TCEB1 functions in cell cycle control while directing cell growth and differentiation which affects renal cell carcinoma advancement.
Association Between TCEB1 Gene Abnormalities and RCC
Some RCC cases exhibit mutations or copy number variations in the TCEB1 gene. The VHL complex's diminished function resulting from TCEB1 loss or mutation increases HIF stability which triggers pro-angiogenic gene expression like VEGF and leads to faster tumor growth.
The Role of TCEB1 in VHL-deficient RCC
Clear cell renal cell carcinoma (ccRCC) primarily develops due to VHL gene mutations which occur in approximately 80% of cases. Among RCC patients who do not have VHL mutations TCEB1 abnormalities can create a secondary mechanism to sustain HIF levels that compensates for VHL function loss.
TCEB1 and Protein Homeostasis Regulation
The E3 ubiquitin ligase complex includes TCEB1 which when dysfunctional can disrupt the breakdown process of various proteins such as:HIF-α (promotes angiogenesis, glycolysis) c-Myc (promotes cell proliferation) p53 (regulates cell cycle and apoptosis)
c-Myc
Through its role in regulating cell cycle and apoptosis p53 increases RCC cell proliferation and metabolic reprogramming while enhancing their resistance to apoptosis.
TCEB1 as a Potential Therapeutic Target
- TCEB1's function as either a tumor suppressor or promoter in RCC varies with specific mutations so its targeted therapy role requires consideration of these effects.
- HIF pathway inhibitors (such as Belzutifan): suitable for RCC patients with VHL/TCEB1 abnormalities.
TCEB1 Is Expected to Become a Target for Renal Cell Carcinoma
The transcription elongation factor B1 (TCEB1) functions as an essential transcriptional regulator that impacts both cellular physiology and response mechanisms while possessing extensive biological importance. TCEB1 affects renal cell carcinoma primarily by impacting the stability of the VHL complex and controlling HIF along with its downstream signaling mechanisms. When TCEB1 experiences mutations or functional loss it results in HIF activation abnormalities which in turn drive tumor angiogenesis and metabolic changes as well as increase cell division rates. The therapeutic targeting of TCEB1 represents a promising strategy for RCC treatment particularly when VHL mutation or loss exists while further investigation is required to understand TCEB1's specific pathophysiological role in RCC. TCEB1 research plays a critical role in understanding the regulation of gene expression and cellular functions along with its involvement in cancer pathogenesis. Further investigation into TCEB1 could reveal innovative approaches for therapeutic development.
References
- Hakimi, A., et al. TCEB1-mutated renal cell carcinoma: a distinct genomic and morphological subtype. Modern Pathology. 2015, 28(6): 845-853.
- Wang, Y., et al. Analysis of clinicopathological and molecular features of ELOC (TCEB1)-mutant renal cell carcinoma. Pathology-Research and Practice. 2022, 235: 153960.
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