Catalysis of non-canonical protein ubiquitylation by the ARIH1 ubiquitin ligase
Biochem J. 2023 Oct 23:BCJ20230373. doi: 10.1042/BCJ20230373. Online ahead of print.ABSTRACTProtein ubiquitylation typically involves isopeptide bond formation between the C-terminus of ubiquitin to the side-chain amino group on Lys residues. However, several ubiquitin ligases (E3s) have recently been identified that ubiquitylate proteins on non-Lys residues. For instance, HOIL-1 belongs to the RING-in-between RING (RBR) class of E3s and has an established role in Ser ubiquitylation. Given the homology between HOIL-1 and ARIH1, an RBR E3 that functions with the large superfamily of cullin-RING E3 ligases (CRLs), a biochemi...
Source: The Biochemical Journal - October 23, 2023 Category: Biochemistry Authors: Nicholas Purser Ishita Tripathi-Giesgen Jerry Li Daniel C Scott Daniel Horn-Ghetko Khee Baek Brenda Schulman Arno Alpi Gary Kleiger Source Type: research

Mitophagy in yeast: known unknowns and unknown unknowns
Biochem J. 2023 Oct 31;480(20):1639-1657. doi: 10.1042/BCJ20230279.ABSTRACTMitophagy, the autophagic breakdown of mitochondria, is observed in eukaryotic cells under various different physiological circumstances. These can be broadly categorized into two types: mitophagy related to quality control events and mitophagy induced during developmental transitions. Quality control mitophagy involves the lysosomal or vacuolar degradation of malfunctioning or superfluous mitochondria within lysosomes or vacuoles, and this is thought to serve as a vital maintenance function in respiring eukaryotic cells. It plays a crucial role in ...
Source: The Biochemical Journal - October 18, 2023 Category: Biochemistry Authors: Hagai Abeliovich Source Type: research

Mitophagy in yeast: known unknowns and unknown unknowns
Biochem J. 2023 Oct 31;480(20):1639-1657. doi: 10.1042/BCJ20230279.ABSTRACTMitophagy, the autophagic breakdown of mitochondria, is observed in eukaryotic cells under various different physiological circumstances. These can be broadly categorized into two types: mitophagy related to quality control events and mitophagy induced during developmental transitions. Quality control mitophagy involves the lysosomal or vacuolar degradation of malfunctioning or superfluous mitochondria within lysosomes or vacuoles, and this is thought to serve as a vital maintenance function in respiring eukaryotic cells. It plays a crucial role in ...
Source: The Biochemical Journal - October 18, 2023 Category: Biochemistry Authors: Hagai Abeliovich Source Type: research

Mitophagy in yeast: known unknowns and unknown unknowns
Biochem J. 2023 Oct 31;480(20):1639-1657. doi: 10.1042/BCJ20230279.ABSTRACTMitophagy, the autophagic breakdown of mitochondria, is observed in eukaryotic cells under various different physiological circumstances. These can be broadly categorized into two types: mitophagy related to quality control events and mitophagy induced during developmental transitions. Quality control mitophagy involves the lysosomal or vacuolar degradation of malfunctioning or superfluous mitochondria within lysosomes or vacuoles, and this is thought to serve as a vital maintenance function in respiring eukaryotic cells. It plays a crucial role in ...
Source: The Biochemical Journal - October 18, 2023 Category: Biochemistry Authors: Hagai Abeliovich Source Type: research

Mitophagy in yeast: known unknowns and unknown unknowns
Biochem J. 2023 Oct 31;480(20):1639-1657. doi: 10.1042/BCJ20230279.ABSTRACTMitophagy, the autophagic breakdown of mitochondria, is observed in eukaryotic cells under various different physiological circumstances. These can be broadly categorized into two types: mitophagy related to quality control events and mitophagy induced during developmental transitions. Quality control mitophagy involves the lysosomal or vacuolar degradation of malfunctioning or superfluous mitochondria within lysosomes or vacuoles, and this is thought to serve as a vital maintenance function in respiring eukaryotic cells. It plays a crucial role in ...
Source: The Biochemical Journal - October 18, 2023 Category: Biochemistry Authors: Hagai Abeliovich Source Type: research

Revisiting the roles of cAMP signalling in the progression of prostate cancer
Biochem J. 2023 Oct 31;480(20):1599-1614. doi: 10.1042/BCJ20230297.ABSTRACTProstate cancer is one of the most common cancers in men and one of the top causes of death in men worldwide. Development and function of both normal prostate cells and early-stage prostate cancer cells are dependent on the cross-talk between androgen signalling systems and a variety of other transduction pathways which drive differentiation of these cells towards castration-resistance. One such signalling pathway is the ubiquitous cAMP signalling axis which functions to activate spatially restricted pools of cAMP effectors such as protein kinase A ...
Source: The Biochemical Journal - October 13, 2023 Category: Biochemistry Authors: Emma C Parsons Ralf Hoffmann George S Baillie Source Type: research

Revisiting the roles of cAMP signalling in the progression of prostate cancer
Biochem J. 2023 Oct 31;480(20):1599-1614. doi: 10.1042/BCJ20230297.ABSTRACTProstate cancer is one of the most common cancers in men and one of the top causes of death in men worldwide. Development and function of both normal prostate cells and early-stage prostate cancer cells are dependent on the cross-talk between androgen signalling systems and a variety of other transduction pathways which drive differentiation of these cells towards castration-resistance. One such signalling pathway is the ubiquitous cAMP signalling axis which functions to activate spatially restricted pools of cAMP effectors such as protein kinase A ...
Source: The Biochemical Journal - October 13, 2023 Category: Biochemistry Authors: Emma C Parsons Ralf Hoffmann George S Baillie Source Type: research

Revisiting the roles of cAMP signalling in the progression of prostate cancer
Biochem J. 2023 Oct 31;480(20):1599-1614. doi: 10.1042/BCJ20230297.ABSTRACTProstate cancer is one of the most common cancers in men and one of the top causes of death in men worldwide. Development and function of both normal prostate cells and early-stage prostate cancer cells are dependent on the cross-talk between androgen signalling systems and a variety of other transduction pathways which drive differentiation of these cells towards castration-resistance. One such signalling pathway is the ubiquitous cAMP signalling axis which functions to activate spatially restricted pools of cAMP effectors such as protein kinase A ...
Source: The Biochemical Journal - October 13, 2023 Category: Biochemistry Authors: Emma C Parsons Ralf Hoffmann George S Baillie Source Type: research

Revisiting the roles of cAMP signalling in the progression of prostate cancer
Biochem J. 2023 Oct 31;480(20):1599-1614. doi: 10.1042/BCJ20230297.ABSTRACTProstate cancer is one of the most common cancers in men and one of the top causes of death in men worldwide. Development and function of both normal prostate cells and early-stage prostate cancer cells are dependent on the cross-talk between androgen signalling systems and a variety of other transduction pathways which drive differentiation of these cells towards castration-resistance. One such signalling pathway is the ubiquitous cAMP signalling axis which functions to activate spatially restricted pools of cAMP effectors such as protein kinase A ...
Source: The Biochemical Journal - October 13, 2023 Category: Biochemistry Authors: Emma C Parsons Ralf Hoffmann George S Baillie Source Type: research

Revisiting the roles of cAMP signalling in the progression of prostate cancer
Biochem J. 2023 Oct 31;480(20):1599-1614. doi: 10.1042/BCJ20230297.ABSTRACTProstate cancer is one of the most common cancers in men and one of the top causes of death in men worldwide. Development and function of both normal prostate cells and early-stage prostate cancer cells are dependent on the cross-talk between androgen signalling systems and a variety of other transduction pathways which drive differentiation of these cells towards castration-resistance. One such signalling pathway is the ubiquitous cAMP signalling axis which functions to activate spatially restricted pools of cAMP effectors such as protein kinase A ...
Source: The Biochemical Journal - October 13, 2023 Category: Biochemistry Authors: Emma C Parsons Ralf Hoffmann George S Baillie Source Type: research

UBE2A/B is the trans-acting factor mediating mechanotransduction and contact inhibition
Biochem J. 2023 Oct 11:BCJ20230208. doi: 10.1042/BCJ20230208. Online ahead of print.ABSTRACTMechanotransduction and contact inhibition (CI) control gene expression to regulate proliferation, differentiation, and even tumorigenesis of cells. However, their downstream trans-acting factors (TAFs) are not well known due to a lack of a high-throughput method to quantitatively detect them. Here, we developed a method to identify TAFs on the cis-acting sequences that reside in open chromatin or DNase I-hypersensitive sites (DHSs) and to detect nucleocytoplasmic shuttling TAFs using computational and experimental screening. The DH...
Source: The Biochemical Journal - October 11, 2023 Category: Biochemistry Authors: Mingwei Feng Jiale Wang Kangjing Li Fumihiko Nakamura Source Type: research

UBE2A/B is the trans-acting factor mediating mechanotransduction and contact inhibition
Biochem J. 2023 Oct 11:BCJ20230208. doi: 10.1042/BCJ20230208. Online ahead of print.ABSTRACTMechanotransduction and contact inhibition (CI) control gene expression to regulate proliferation, differentiation, and even tumorigenesis of cells. However, their downstream trans-acting factors (TAFs) are not well known due to a lack of a high-throughput method to quantitatively detect them. Here, we developed a method to identify TAFs on the cis-acting sequences that reside in open chromatin or DNase I-hypersensitive sites (DHSs) and to detect nucleocytoplasmic shuttling TAFs using computational and experimental screening. The DH...
Source: The Biochemical Journal - October 11, 2023 Category: Biochemistry Authors: Mingwei Feng Jiale Wang Kangjing Li Fumihiko Nakamura Source Type: research

Microrchidia 2/Histone Deacetylase 1 Complex Regulates E-cadherin Gene Expression and Function
Biochem J. 2023 Oct 10:BCJ20230304. doi: 10.1042/BCJ20230304. Online ahead of print.ABSTRACTAlthough Microrchidia 2 (MORC2) is widely overexpressed in human malignancies and linked to cancer cell proliferation, metabolism, and metastasis, the mechanism of action of MORC2 in cancer cell migration and invasion is yet undeciphered. Here, we identified for the first time that MORC2, a chromatin remodeler, regulates E-cadherin expression and, subsequently regulates breast cancer cell migration and invasion. We observed a negative correlation between the expression levels of MORC2 and E-cadherin in breast cancer. Further, the ov...
Source: The Biochemical Journal - October 10, 2023 Category: Biochemistry Authors: Liz Thomas Namita Chutani Krishna R Asha S Nair Nanda Kumar Yellapu Karyala Prashanthi Suresh Babu Pakala Source Type: research

Microrchidia 2/Histone Deacetylase 1 Complex Regulates E-cadherin Gene Expression and Function
Biochem J. 2023 Oct 10:BCJ20230304. doi: 10.1042/BCJ20230304. Online ahead of print.ABSTRACTAlthough Microrchidia 2 (MORC2) is widely overexpressed in human malignancies and linked to cancer cell proliferation, metabolism, and metastasis, the mechanism of action of MORC2 in cancer cell migration and invasion is yet undeciphered. Here, we identified for the first time that MORC2, a chromatin remodeler, regulates E-cadherin expression and, subsequently regulates breast cancer cell migration and invasion. We observed a negative correlation between the expression levels of MORC2 and E-cadherin in breast cancer. Further, the ov...
Source: The Biochemical Journal - October 10, 2023 Category: Biochemistry Authors: Liz Thomas Namita Chutani Krishna R Asha S Nair Nanda Kumar Yellapu Karyala Prashanthi Suresh Babu Pakala Source Type: research

The choreography of protein kinase PDK1 and its diverse substrate dance partners
Biochem J. 2023 Oct 11;480(19):1503-1532. doi: 10.1042/BCJ20220396.ABSTRACTThe protein kinase PDK1 phosphorylates at least 24 distinct substrates, all of which belong to the AGC protein kinase group. Some substrates, such as conventional PKCs, undergo phosphorylation by PDK1 during their synthesis and subsequently get activated by DAG and Calcium. On the other hand, other substrates, including members of the Akt/PKB, S6K, SGK, and RSK families, undergo phosphorylation and activation downstream of PI3-kinase signaling. This review presents two accepted molecular mechanisms that determine the precise and timely phosphorylati...
Source: The Biochemical Journal - October 4, 2023 Category: Biochemistry Authors: Alejandro E Leroux Ricardo M Biondi Source Type: research