TGFB2

Fig1. Overview of currently known TGFB2 mutations. (Marco Ritelli, 2014)

What is TGFB2 protein?

TGFB2 (transforming growth factor beta 2) gene is a protein coding gene which situated on the long arm of chromosome 1 at locus 1q41. Transforming growth factor betas (TGF betas) mediate many cell-cell interactions that occur during embryonic development. Three TGFbs have been identified in mammals. TGF beta1, TGF beta2 and TGF beta3 are each synthesized as precursor proteins that are very similar in that each is cleaved to yield a 112 amino acid polypeptide that remains associated with the latent portion of the molecule. The TGFB2 protein is consisted of 414 amino acids and its molecular mass is approximately 47.7 kDa.

What is the function of TGFB2 protein?

TGFB2(Transforming Growth Factor-β2) is a multifunctional cytokine belonging to the TGF-β superfamily. It is mainly involved in the regulation of cell proliferation, differentiation, migration and apoptosis. TGFB2 plays an important role in embryonic development, tissue repair, immune regulation, and disease occurrence and progression. By binding to specific receptors, TGFB2 activates the SMAD signaling pathway, which in turn affects gene expression and cell behavior.

TGFB2 Related Signaling Pathway

TGF-β signaling pathway: TGFB2 is a member of the TGF-β family and participates in the TGF-β signaling pathway. TGF-β receptor regulates cell proliferation, differentiation, apoptosis and other biological functions by activating Smad protein.

MAPK/ERK signaling pathway: TGFB2 can also regulate biological processes such as cell growth, differentiation, and transcription by activating the MAPK/ERK signaling pathway.

PI3K/AKT signaling pathway: TGFB2 may also participate in the PI3K/AKT signaling pathway, regulating biological functions such as cell survival, proliferation and cycle.

TGFB2 Related Diseases

Mutations or defects in the TGFB2 gene may lead to the development of some genetic diseases, such as Marfan syndrome. TGFB2 is closely related to the occurrence and development of various tumors such as breast cancer, gastric cancer and ovarian cancer. In some cases, TGFB2 can promote or inhibit tumor growth and metastasis. TGFB2 protein is also involved in the control of inflammatory response and immune disease. TGFB2 plays an important role in embryonic development, and abnormal TGFB2 signal may lead to fetal development defects, such as mouth cleft and heart malformation.

Bioapplications of TGFB2

TGFB2 can promote wound healing and tissue repair, so it has potential applications in the field of trauma medicine and tissue repair. TGFB2 can be used as a biomarker for certain diseases for diagnosis and disease surveillance. TGFβ inhibitors are being investigated for cancer treatment.

Case study 1: Xiao-Ming Jiang, 2021

Osimertinib (AZD9291) has been widely used for the treatment of EGFR mutant non-small cell lung cancer. However, resistance to osimertinib is inevitable. In this study the researchers elucidated the molecular mechanisms of resistance in osimertinib-resistant NCI-H1975/OSIR cells. In NCI-H1975 cells, osimertinib activated NF-κB pathway, evidenced by the increased p65 nuclear translocation, which was abolished by knockdown of TGFβ2. In the cancer genome atlas lung adenocarcinoma data, TGFB2 transcript abundance significantly correlated with EMT-associated genes and NF-κB pathway. These findings shed new light on distinct roles of TGFβ2 in osimertinib-resistant cells and provide new strategies for treatment of this resistant status.

Fig1. The indicated protein levels were determined by Western blotting after cotreatment with the TGFβRI inhibitor SB525334 (SB, 1 μM) and OSI (125 nM) for 48 h.

Fig2. Immunofluorescence assay was performed to analyze the expression and localization of p65 in NCI-H1975 cells with silenced TGFB2 for 24 h, followed by treatment with OSI for another 48 h.

Case study 2: Jinliang Wu, 2017

The metabolic reprogramming is indispensible for the fast growth of tumor cells. The metabolism of CAFs is reprogrammed to aerobic glycolysis too. However, it is not clear whether this metabolic reprogramming promotes the growth of CAFs themselves.

The researchers found TGF-β signaling regulated cell growth of CAF through RNA-sequencing analysis and Western blot, which was further supported by the observation that TGF-β2 was highly expressed in colon cancer tissues. In brief, the data have manifested that the proliferation rate is decreased in CAFs, which enable CAFs generate more intermediate metabolites to support tumor cells growth, suggesting CAFs is an ideal target for tumor therapy.

Fig3. Verification of the possible pathway regulating G1/S checkpoint.

Fig4. The expression of TGF-β2 in colon cancer tissue. FSP1 is a marker of CAF.

TGFB2 has several biochemical functions, for example, beta-amyloid binding,cytokine activity,growth factor activity. Some of the functions are cooperated with other proteins, some of the functions could acted by TGFB2 itself. We selected most functions TGFB2 had, and list some proteins which have the same functions with TGFB2. You can find most of the proteins on our site.

TGFB2 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with TGFB2 here. Most of them are supplied by our site. Hope this information will be useful for your research of TGFB2.

APP;BMP2