ASURA (PHB2) Is Required for Kinetochore Assembly and Subsequent Chromosome Congression

Abstract

ASURA (PHB2) knockdown has been known to cause premature loss of sister chromatid cohesion, and disrupt the localization of several outer plate proteins to the kinetochore. As a result, cells are arrested at mitotic phase and chromosomes fail to congress to the metaphase plate. In this study, we further clarified the mechanism underlying ASURA function on chromosome congression. Interestingly, ASURA is not specifically localized at the kinetochore during mitotic phase, unlike other kinetochore proteins which construct the kinetochore. Electron microscopy (EM) observation showed that ASURA is required for proper kinetochore formation. By the partial depletion of ASURA, kinetochore maturation is impaired, and kinetochores showing fibrillar balls without a well-defined outer plates are often observed. Moreover, even when the outer plates of kinetochores are constructed, most showed structures stretched and/or distended from the centromere, which resembled premature kinetochores at prometaphase, indicating that the constructed kinetochore plates are less rigid against tension derived from kinetochore microtubule pulling forces. We concluded that ASURA is an essential protein for complete kinetochore development, although ASURA is not being integrated to the kinetochore. These results highlight the uniqueness of ASURA as a kinetochore protein.

ASURA (PHB2) Interacts with Scc1 through Chromatin

“…We found both ASURA and Scc1 localized in the nuclei throughout interphase, although ASURA was also detected in the cytoplasm as shown in our previous study [Lee et al, 2011]. At prophase, both proteins co-localized on chromatin; ASURA and Scc1 then dissociated to the cytoplasm during metaphase and anaphase.…”

“…These proteins have a homologous structural domain called the SPFH (stomatin, prohibitin, flotillin, and HflC/K) domain which is also known as the PHB domain [Mishra et al, 2006]. PHB2, also called ASURA [Lee et al, 2011], and its related protein PHB1, were originally described as negative regulators of cell proliferation, from which the name prohibitin is derived [Nuell et al, 1991]. ASURA localizes at multiple cellular compartments, including the cell membrane, mitochondria, and nucleus, providing diverse cellular functions.…”

Proteomic analysis of liver mitochondria of db/db mice treated with grape seed procyanidin B2

“…PHB2, as an autophagy receptor in the inner mitochondrial membrane, is not only involved in cell cycle regulation, transcriptional regulation, cell proliferation and apoptosis, signal transduction, and other cellular processes, but also involved in targeted mitochondrial autophagy and degradation (Osman, Merkwirth, & Langer, 2009; Ross, Nagy, & Kirken, 2008; Steglich, Neupert, & Langer, 1999). PHB2 plays an important role in cell cycle progression and aging, as well as in many diseases such as obesity, diabetes, and cancer (Lee et al., 2011). Ubiquinone biosynthesis protein COQ9 is a lipid‐soluble protein of the electron transport chain involved in the biosynthesis of coenzyme Q.…”

“…Our (Osman, Merkwirth, & Langer, 2009;Ross, Nagy, & Kirken, 2008;Steglich, Neupert, & Langer, 1999). PHB2 plays an important role in cell cycle progression and aging, as well as in many diseases such as obesity, diabetes, and cancer (Lee et al, 2011). Ubiquinone biosynthesis protein COQ9 is a lipid-soluble protein of the electron transport chain involved in the biosynthesis of coenzyme Q.…”

Identification of a panel of complex autoantigens (LGALS3, PHB2, MUC1, and GK2) in combination with CA15-3 for the diagnosis of early-stage breast cancer

“…These antigens were found to play important roles in both initiation and progression of malignancies. CA15-3 is the most widely used antigen in monitoring BC and for the early diagnosis of BC metastasis [3]; LGALS3 expression appears to be a predictive factor for the aggressive behavior of pituitary adenomas [9], is an important biomarker in prostate cancer, plays important roles in the progression of prostate cancer [6,7], promotes the progression of colon cancer and cerebellar hemangioblastoma [8,10], and correlates with the apoptosis of BC cells [11]; PHB2 localizes to the inner mitochondrial membrane, is a member of the prohibitin family, plays a role in platelet aggregation, kinetochore assembly, BC cell proliferation, and adhesion [12][13][14], and supports the development and progression of hepatocellular carcinoma by adapting to hypoxic microenvironments and resisting chemotherapy-induced apoptosis [15]; ANKRD30A is similar to BC antigen NY-BR-1, which is a differentiated antigen of the mammary gland [16].…”