55233

MOB1A

C2orf6|MATS1|MOB1|MOBK1B|MOBKL1B|Mob4B;MOB kinase activator 1A;MOB1A;MOB kinase activator 1A

MOB1 Mps One Binder homolog A|MOB1, Mps One Binder kinase activator-like 1B|mob1 alpha|mob1 homolog 1B|mps one binder kinase activator-like 1B

2p13.1

protein-coding

Count: 2; Pubmed_search,Generif

MOB (Mps one binder) was originally identified in yeast as a regulator of mitotic exit and cytokinesis, and was later identified as a tumor suppressor and a component of an emerging Hippo-LATS tumor suppressor pathway in Drosophila (D). So far, 7 human homologs of yeast MOB (hMOB1A, 1B, 2A, 2B, 2C, 3, 4) have been identified. Although hMOB1A/B has been extensively studied, the biological features of other hMOBs are largely unknown. In addition, while hMOB1 has been reported to interact with and activate LATS (Large tumor suppressor)/Warts tumor suppressor, the functional significance of this is unknown. In this study, we have characterized, for the first time, the cellular and biochemical function of all human MOBs. By examining hMOB mRNAs expression in various human tissues, we found that hMOBs demonstrated different expression patterns. Further biochemical characterization of hMOBs showed that only hMOB1A and hMOB1B interact with both LATS1 and LATS2 in vitro and in vivo. Significantly, we have discovered that overexpression of hMOB1 in human cancer cells activated LATS activity and inhibited cell proliferation or caused apoptosis while hMOB1, targeting the plasma membrane, led to a more significant phenotype. Reciprocally, short-hairpin (sh) RNA-mediated suppression of hMOB1 causes increased cell proliferation. Our findings provided evidence that hMOB1A and hMOB1B are 2 LATS-binding proteins that may function as tumor suppressors in human cancer cells.

Appropriate cell number and organ size in a multicellular organism are determined by coordinated cell growth, proliferation, and apoptosis. Disruption of these processes can cause cancer. Recent studies have identified the Large tumor suppressor (Lats)/Warts (Wts) protein kinase as a key component of a pathway that controls the coordination between cell proliferation and apoptosis. Here we describe growth inhibitory functions for a Mob superfamily protein, termed Mats (Mob as tumor suppressor), in Drosophila. Loss of Mats function results in increased cell proliferation, defective apoptosis, and induction of tissue overgrowth. We show that mats and wts function in a common pathway. Mats physically associates with Wts to stimulate the catalytic activity of the Wts kinase. A human Mats ortholog (Mats1) can rescue the lethality associated with loss of Mats function in Drosophila. As Mats1 is mutated in human tumors, Mats-mediated growth inhibition and tumor suppression is likely conserved in humans.